N-[3-[(2R,3R,4R,5R)-5-[[bis(4-methoxyphenyl)-phenylmethoxy]methyl]-2-(2,4-dioxopyrimidin-1-yl)-4-hydroxyoxolan-3-yl]oxypropyl]-2,2,2-trifluoroacetamide | 165381-48-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: N-[3-[(2R,3R,4R,5R)-5-[[bis(4-methoxyphenyl)-phenylmethoxy]methyl]-2-(2,4-dioxopyrimidin-1-yl)-4-hydroxyoxolan-3-yl]oxypropyl]-2,2,2-trifluoroacetamide
• CAS: 165381-48-6
• 化学式: C₃₅H₃₆F₃N₃O₉
• 分子量: 699.681
• InChiKey: XXRWNEIKDDVHRB-PMFUCWTESA-N

物化性质

• 密度：
  1.41±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  50
• 可旋转键数：
  14
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.34
• 拓扑面积：
  145
• 氢给体数：
  3
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  2-氰乙基N,N-二异丙基氯亚磷酰胺 、 N-[3-[(2R,3R,4R,5R)-5-[[bis(4-methoxyphenyl)-phenylmethoxy]methyl]-2-(2,4-dioxopyrimidin-1-yl)-4-hydroxyoxolan-3-yl]oxypropyl]-2,2,2-trifluoroacetamide 在 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 以36%的产率得到N-[3-[(2R,3R,4R,5R)-5-[[bis(4-methoxyphenyl)-phenylmethoxy]methyl]-4-[2-cyanoethoxy-[di(propan-2-yl)amino]phosphanyl]oxy-2-(2,4-dioxopyrimidin-1-yl)oxolan-3-yl]oxypropyl]-2,2,2-trifluoroacetamide
  参考文献：
  名称：

  [EN] EXTRAHEPATIC DELIVERY
  [FR] ADMINISTRATION EXTRA-HÉPATIQUE

  摘要：

  公开号：

  WO2021092371A3
• 作为产物：
  描述：

  2'-O-(3-phthalimidopropyl)uridine 在 吡啶 、 三乙胺 、 肼 作用下， 以 甲醇 、 乙醇 为溶剂， 反应 48.0h， 生成 N-[3-[(2R,3R,4R,5R)-5-[[bis(4-methoxyphenyl)-phenylmethoxy]methyl]-2-(2,4-dioxopyrimidin-1-yl)-4-hydroxyoxolan-3-yl]oxypropyl]-2,2,2-trifluoroacetamide
  参考文献：
  名称：

  2‘-O-Aminopropyl Ribonucleotides:  A Zwitterionic Modification That Enhances the Exonuclease Resistance and Biological Activity of Antisense Oligonucleotides

  摘要：

  Oligonucleotides containing 2'-O-aminopropyl-substituted RNA have been synthesized. The 2'-O-(aminopropyl)adenosine (APA), 2'-O-(aminopropyl)cytidine (APC), 2'-O-(aminopropyl)guanosine (APG), and 2'-O-(aminopropyl)uridine (APU) have been prepared in high yield from the ribonucleoside, protected, and incorporated into an oligonucleotide using conventional phosphoramidite chemistry. Molecular dynamics studies of a dinucleotide in water demonstrates that a short alkylamine located off the 2'-oxygen of ribonucleotides alters the sugar pucker of the nucleoside but does not form a tight ion pair with the proximate phosphate. A 5-mer with the sequence ACTUC has been characterized using NMR. As predicted from the modeling results, the sugar pucker of the APU moiety is shifted toward a C3'-endo geometry. In addition, the primary amine rotates freely and is not bound electrostatically to any phosphate group, as evidenced by the different sign of the NOE between sugar proton resonances and the signals from the propylamine chain. Incorporation of aminopropyl nucleoside residues into point-substituted and fully modified oligomers does not decrease the affinity for complementary RNA compared to 2'-O-alkyl substituents of the same length. However, two APU residues placed at the 3'-terminus of an oligomer gives a 100-fold increase in resistance to exonuclease degradation, which is greater than observed for phosphorothioate oligomers. These structural and biophysical characteristics make the 2'-O-aminopropyl group a leading choice for incorporation into antisense therapeutics. A 20-mer phosphorothioate oligonucleotide capped with two phosphodiester aminopropyl nucleotides targeted against C-raf mRNA has been transfected into cells via electroporation. This oligonucleotide has 5-10-fold greater activity than the control phosphorothioate for reducing the abundance of C-raf mRNA and protein.

  DOI：

  10.1021/jm950937o

文献信息

• [EN] TRANSTHYRETIN (TTR) IRNA COMPOSITIONS AND METHODS OF USE THEREOF FOR TREATING OR PREVENTING TTR-ASSOCIATED OCULAR DISEASES<br/>[FR] COMPOSITION D'ARNI DE LA TRANSTHYRÉTINE (TTR) ET SES PROCÉDÉS D'UTILISATION POUR LE TRAITEMENT OU LA PRÉVENTION DE MALADIES OCULAIRES ASSOCIÉES À TTR
  申请人：ALNYLAM PHARMACEUTICALS INC

  公开号：WO2021092145A8

  公开（公告）日：2021-07-08
• AMINE-DERIVATIZED NUCLEOSIDES AND OLIGONUCLEOSIDES
  申请人：ISIS PHARMACEUTICALS, INC.

  公开号：EP0728139A1

  公开（公告）日：1996-08-28
• US7037646B1
  申请人：——

  公开号：US7037646B1

  公开（公告）日：2006-05-02
• [EN] AMINE-DERIVATIZED NUCLEOSIDES AND OLIGONUCLEOSIDES<br/>[FR] NUCLEOSIDES ET OLIGONUCLEOSIDES A FONCTION(S) AMINE
  申请人：ISIS PHARMACEUTICALS, INC.

  公开号：WO1995006659A1

  公开（公告）日：1995-03-09

  (EN) Nucleosides and oligonucleosides functionalized to include alkylamino functionality, and derivatives thereof. In certain embodiments, the compounds of the invention further include steroids, reporter molecules, reporter enzymes, lipophilic molecules, peptides or proteins attached to the nucleosides through the alkylamino group.(FR) L'invention concerne des nucléosides et des oligonucléosides modifiés par l'adjonction de fonctions alkylamino, ainsi que leurs dérivés. Dans certaines formes d'exécution, les composés de l'invention comportent en outre des stéroïdes, des molécules reporteurs, des enzymes reporteurs, des molécules lipophiles, des peptides ou des protéines, fixés aux nucléosides par le groupe alkylamino.
• [EN] EXTRAHEPATIC DELIVERY<br/>[FR] ADMINISTRATION EXTRA-HÉPATIQUE
  申请人：ALNYLAM PHARMACEUTICALS INC

  公开号：WO2021092371A3

  公开（公告）日：2021-06-17