S-[2-bis(diisopropylamino)phosphanyloxyethyl]-2,2-dimethyl-3-trityloxy-propanethioate | 1192047-83-8

• 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: S-[2-bis(diisopropylamino)phosphanyloxyethyl]-2,2-dimethyl-3-trityloxy-propanethioate
• 英文别名: S-(2,2-dimethyl-3-triphenylmethoxypropionyl)-2-thioethyl-di(N,N-diisopropylamino)phosphorobisamidite；S-[2-bis[di(propan-2-yl)amino]phosphanyloxyethyl] 2,2-dimethyl-3-trityloxypropanethioate
• CAS: 1192047-83-8
• 化学式: C₃₈H₅₅N₂O₃PS
• 分子量: 650.906
• InChiKey: ZXCJBBZWWQXBRY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.5
• 重原子数：
  45
• 可旋转键数：
  18
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  67.3
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  S-[2-bis(diisopropylamino)phosphanyloxyethyl]-2,2-dimethyl-3-trityloxy-propanethioate 在 吡啶 、 四氮唑 、 三氟乙酸 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 0.17h， 生成 S-[2-[[(4aR,6R,7R,7aR)-6-(2-amino-6-ethoxypurin-9-yl)-7-hydroxy-7-methyl-2-oxo-4,4a,6,7a-tetrahydrofuro[3,2-d][1,3,2]dioxaphosphinin-2-yl]oxy]ethyl] 3-hydroxy-2,2-dimethylpropanethioate
  参考文献：
  名称：

  3',5'-CYCLIC PHOSPHATE PRODRUGS FOR HCV INFECTION

  摘要：

  本文提供了用于治疗黄病毒科感染，包括HCV感染的化合物、组合物和方法。在某些实施例中，披露了核苷类衍生物的化合物和组合物，可以单独或与其他抗病毒药物联合使用。

  公开号：

  US20130315867A1
• 作为产物：
  描述：

  2,2-dimethyl-3-(trityloxy)propanoic acid 、 双二异丙基氨基氯化磷 在 三乙胺 作用下， 以 乙醚 为溶剂， 反应 5.0h， 以100%的产率得到S-[2-bis(diisopropylamino)phosphanyloxyethyl]-2,2-dimethyl-3-trityloxy-propanethioate
  参考文献：
  名称：

  3',5'-CYCLIC PHOSPHATE PRODRUGS FOR HCV INFECTION

  摘要：

  本文提供了用于治疗黄病毒科感染，包括HCV感染的化合物、组合物和方法。在某些实施例中，披露了核苷类衍生物的化合物和组合物，可以单独或与其他抗病毒药物联合使用。

  公开号：

  US20130315867A1

文献信息

• The discovery of IDX21437: Design, synthesis and antiviral evaluation of 2′-α-chloro-2′-β-C-methyl branched uridine pronucleotides as potent liver-targeted HCV polymerase inhibitors
  作者：François-René Alexandre、Eric Badaroux、John P. Bilello、Stéphanie Bot、Tony Bouisset、Guillaume Brandt、Sylvie Cappelle、Christopher Chapron、Dominique Chaves、Thierry Convard、Clément Counor、Daniel Da Costa、David Dukhan、Marion Gay、Gilles Gosselin、Jean-François Griffon、Kusum Gupta、Brenda Hernandez-Santiago、Massimiliano La Colla、Marie-Pierre Lioure、Julien Milhau、Jean-Laurent Paparin、Jérôme Peyronnet、Christophe Parsy、Claire Pierra Rouvière、Houcine Rahali、Rachid Rahali、Aurélien Salanson、Maria Seifer、Ilaria Serra、David Standring、Dominique Surleraux、Cyril B. Dousson

  DOI：10.1016/j.bmcl.2017.08.029

  日期：2017.9

  Herein we describe the discovery of IDX21437 35b, a novel RP d-aminoacid-based phosphoramidate prodrug of 2′-α-chloro-2′-β-C-methyluridine monophosphate. Its corresponding triphosphate 6 is a potent inhibitor of the HCV NS5B RNA-dependent RNA polymerase (RdRp). Despite showing very weak activity in the in vitro Huh-7 cell based HCV replicon assay, 35b demonstrated high levels of active triphosphate 6 in

  在此，我们描述了 IDX21437 35b的发现，它是一种新型的基于R P d -氨基酸的氨基磷酸酯前药，它是 2'-α-氯-2'-β- C-甲基尿苷单磷酸酯。其相应的三磷酸6是 HCV NS5B RNA 依赖性 RNA 聚合酶 (RdRp) 的有效抑制剂。尽管在体外基于 Huh-7 细胞的 HCV 复制子测定中显示出非常弱的活性，但35b在小鼠肝脏和人肝细胞中显示出高水平的活性三磷酸6。一项生化研究表明，35b的代谢主要归因于羧酸酯酶 1 (CES1)，这是一种在 HCV Huh-7 衍生的复制子细胞中表达不足的酶。此外，由于其代谢活化，与其他细胞类型（包括人心肌细胞）相比，35b在肝细胞中得到有效加工。选定的35b 的R P非对映异构体构型由 X 射线结构测定确定。35b目前正处于治疗 HCV 感染的 II 期临床试验中。
• 2'-CHLORO NUCLEOSIDE ANALOGS FOR HCV INFECTION
  申请人：Idenix Pharmaceuticals, Inc.

  公开号：US20160083413A1

  公开（公告）日：2016-03-24

  Provided herein are compounds, compositions and methods for the treatment of Flaviviridae infections, including HCV infections. In certain embodiments, compounds and compositions of nucleoside derivatives are disclosed, which can be administered either alone or in combination with other anti-viral agents. In certain embodiments, the compounds are 2′-chloro nucleosides according to Formula 2001: or a pharmaceutically acceptable salt, solvate, stereoisomeric form, tautomeric form or polymorphic form thereof, wherein B, Z and PD are as described herein.

  本文提供了用于治疗黄病毒科感染，包括丙型肝炎(HCV)感染的化合物、组合物和方法。在某些实施例中，公开了核苷衍生物的化合物和组合物，可以单独或与其他抗病毒药物联合使用。在某些实施例中，化合物是根据公式2001的2'-氯核苷，或其药学上可接受的盐、溶剂化合物、立体异构体形式、互变异构体形式或多态形式，其中B、Z和PD如本文所述。
• Special feature of mixed phosphotriester derivatives of cytarabine
  作者：Marie-Hélène Gouy、Lars P. Jordheim、Isabelle Lefebvre、Emeline Cros、Charles Dumontet、Suzanne Peyrottes、Christian Périgaud

  DOI：10.1016/j.bmc.2009.07.038

  日期：2009.9.1

  Despite the unquestionable therapeutic interest of bis(SATE) pronucleotides, a presystemic metabolism preventing the delivery of the prodrugs in target cancer cells or tumours may constitute a limitation to the in vivo development of such derivatives. In order to overcome these drawbacks several strategies have been envisaged and we report herein the application of the S-acyl-2-thioethyl (SATE) phenyl pronucleotide approach to the well-known cytotoxic nucleoside cytosine-1-beta-D-arabinofuranoside (cytarabine, araC). We describe modifications of the SATE moieties with the introduction of polar groups on the acyl residue, in order to study how these changes affect antitumoral activity and metabolic stability. Two different synthetic pathways were explored and lead to obtain the corresponding mixed derivatives in satisfactory yields. Cytotoxicity was studied in murine leukaemia cells L1210 as well as in cells derived from solid human tumours (Messa and MCF7). Biological evaluation of these compounds in cell culture experiments with nucleoside analogue-sensitive and resistant cell lines showed that the modified compounds were active at higher concentrations than unmodified cytarabine, yet were much able to partially reverse resistance due to deficient nucleoside transport or activation. These results can be correlated with an incomplete decomposition mechanism into the corresponding 5'-mononucleotide. (C) 2009 Elsevier Ltd. All rights reserved.
• US9296778B2
  申请人：——

  公开号：US9296778B2

  公开（公告）日：2016-03-29
• [EN] 2'-CHLORO NUCLEOSIDE ANALOGS FOR HCV INFECTION<br/>[FR] ANALOGUES DE NUCLÉOSIDES 2'-CHLORO POUR TRAITER UNE INFECTION PAR LE VIRUS DE L'HÉPATITE C
  申请人：IDENIX PHARMACEUTICALS INC

  公开号：WO2014058801A1

  公开（公告）日：2014-04-17

  Provided herein are compounds, compositions and methods for the treatment of Flaviviridae infections, including HCV infections. In certain embodiments, compounds and compositions of nucleoside derivatives are disclosed, which can be administered either alone or in combination with other anti-viral agents. In certain embodiments, the compounds are 2'-chloro nucleosides according to Formula 2001: (2001); or a pharmaceutically acceptable salt, solvate, stereoisomeric form, tautomeric form or polymorphic form thereof, wherein B, Z and PD are as described herein.