[3S,4S]-1-N-Boc-3-dimethoxytrityloxy-4-hydroxypyrrolidine | 926913-07-7

• 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: [3S,4S]-1-N-Boc-3-dimethoxytrityloxy-4-hydroxypyrrolidine
• 英文别名: (3S,4S)-tert-butyl 3-(bis(4-methoxyphenyl)(phenyl)methoxy)-4-hydroxypyrrolidine-1-carboxylate；tert-butyl (3S,4S)-3-[bis(4-methoxyphenyl)-phenylmethoxy]-4-hydroxypyrrolidine-1-carboxylate
• CAS: 926913-07-7
• 化学式: C₃₀H₃₅NO₆
• 分子量: 505.611
• InChiKey: CVBNBHLLSHTNKI-SVBPBHIXSA-N

物化性质

• 沸点：
  618.9±55.0 °C(Predicted)
• 密度：
  1.22±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  37
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  77.5
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  [3S,4S]-1-N-Boc-3-dimethoxytrityloxy-4-hydroxypyrrolidine 在 4-二甲氨基吡啶 、 caesium carbonate 作用下， 以 二氯甲烷 、 二甲基亚砜 为溶剂， 反应 97.0h， 生成 (3S,4R)-4-(adenin-9-yl)-1-N-tert-butyloxycarbonyl-3-(4,4'-dimethoxytrityloxy)pyrrolidine
  参考文献：
  名称：

  Synthesis of diastereomeric 3-hydroxy-4-pyrrolidinyl derivatives of nucleobases

  摘要：

  The work deals with the synthesis of hydroxypyrrolidine analogs of nucleosides. Starting from the optically pure L- or D-tartaric acid, we improved the synthesis of enantiomeric trans-3,4-dihydroxypyrrolidines and elaborated a procedure for the synthesis of all possible diastereoisomers of 3-hydroxy-4-pyrrolidinyl derivatives of both purine and pyrimidine nucleobases. The prepared compounds were tested for cytostatic and antiviral properties but no significant activity was found. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2006.11.047
• 作为产物：
  描述：

  甲酸叔丁酯 在 吡啶 、 4-二甲氨基吡啶 、 三乙胺 作用下， 以 甲醇 为溶剂， 反应 22.0h， 生成 [3S,4S]-1-N-Boc-3-dimethoxytrityloxy-4-hydroxypyrrolidine
  参考文献：
  名称：

  [EN] TRIAZOLOPYRIDINE COMPOUNDS AS PIM KINASE INHIBITORS
  [FR] COMPOSÉS DE TRIAZOLOPYRIDINE EN TANT QU'INHIBITEURS DE KINASE PIM

  摘要：

  式I的化合物：其中R1、R2、R3、R4和R10的含义如规范中所述，在通过PIM-1和/或PIM-2和/或PIM-3激酶介导的疾病治疗中有用的受体酪氨酸激酶抑制剂。

  公开号：

  WO2012154274A1

文献信息

• [EN] 6-OXOPURINE PHOSPHORIBOSYL TRANSFERASE INHIBITORS<br/>[FR] INHIBITEURS DES 6-OXOPURINE PHOSPHORIBOSYLTRANSFÉRASES
  申请人：UNIV QUEENSLAND

  公开号：WO2017100849A1

  公开（公告）日：2017-06-22

  The invention relates to compounds which are useful as inhibitors of 6-oxopurine phosphoribosyltransferases such as hypoxanthine-guanine-(xanthine) phosphoribosyltransferase (HG(X)PRT).

  这项发明涉及作为6-氧杂嘌呤磷酸核糖转移酶抑制剂的化合物，例如次黄嘌呤-鸟嘌呤-(黄嘌呤)磷酸核糖转移酶（HG(X)PRT）。
• Synthesis, conformational studies, and biological properties of phosphonomethoxyethyl derivatives of nucleobases with a locked conformation via a pyrrolidine ring
  作者：Radek Pohl、Lenka Poštová Slavětínská、Wai Soon Eng、Dianne T. Keough、Luke W. Guddat、Dominik Rejman

  DOI：10.1039/c5ob00097a

  日期：——

  structure–activity studies on a diverse family of nucleoside phosphonic acids has led to the development of potent antiviral drugs such as HPMPC (CidofovirTM), PMEA (AdefovirTM), and PMPA (TenofovirTM), which are used in the treatment of CMV-induced retinitis, hepatitis B, and HIV, respectively. Here, we present the synthesis of a novel class of acyclic phosphonate nucleotides that have a locked conformation

  对多种核苷膦酸家族的系统结构活性研究导致开发了有效的抗病毒药物，例如HPMPC（CidofovirTM），PMEA（AdefovirTM）和PMPA（TenofovirTM），这些药物用于治疗CMV诱导的视网膜炎，乙型肝炎和艾滋病毒。在这里，我们提出了一种新型的无环膦酸酯核苷酸的合成，其通过吡咯烷环具有锁定的构象。这些化合物的NMR分析表明，当吡咯烷环通过氢键成pD ＜10时为顺式时，其具有受约束的构象。测试了这些化合物中的四种作为人和恶性疟原虫的抑制剂6-氧嘌呤磷酸核糖基转移酶。最有效的恶性疟原虫HGXPRT的K i为0.6μM。
• Triazolopyridine compounds as PIM kinase inhibitors
  申请人：Blake James F.

  公开号：US08889704B2

  公开（公告）日：2014-11-18

  Compounds of Formula I: in which R1, R2, R3, R4 and R10 have the meanings given in the specification, are receptor tyrosine inhibitors useful in the treatment of diseases mediated by PIM-1 and/or PIM-2 and/or PIM-3 kinases.

  公式I的化合物：其中R1、R2、R3、R4和R10具有规范中给出的含义，是在治疗由PIM-1和/或PIM-2和/或PIM-3激酶介导的疾病中有用的受体酪氨酸激酶抑制剂。
• TRIAZOLOPYRIDINE COMPOUNDS AS PIM KINASE INHIBITORS
  申请人：Blake James F.

  公开号：US20140005213A1

  公开（公告）日：2014-01-02

  Compounds of Formula I: in which R 1 , R 2 , R 3 , R 4 and R 10 have the meanings given in the specification, are receptor tyrosine inhibitors useful in the treatment of diseases mediated by PIM-1 and/or PIM-2 and/or PIM-3 kinases.

  式I的化合物：其中R1、R2、R3、R4和R10具有规范中给出的含义，是可用于治疗由PIM-1和/或PIM-2和/或PIM-3激酶介导的疾病的受体酪氨酸激酶抑制剂。
• Pyrrolidine nucleoside bisphosphonates as antituberculosis agents targeting hypoxanthine-guanine phosphoribosyltransferase
  作者：Wai Soon Eng、Dominik Rejman、Radek Pohl、Nicholas P. West、Kyra Woods、Lieve M.J. Naesens、Dianne T. Keough、Luke W. Guddat

  DOI：10.1016/j.ejmech.2018.09.039

  日期：2018.11

  Therapeutic treatment of tuberculosis (TB) is becoming increasingly problematic due to the emergence of drug resistant Mycobacterium tuberculosis (Mt). Thus, new targets for anti-TB drug discovery need to be identified to combat and eradicate this disease. One such target is hypoxanthine-guanine phosphoribosyltransferase (HGPRT) which synthesises the 6-oxopurine nucleoside monophosphates essential for DNA/RNA production. [3R,4R]-4-Hypoxanthin-9-yl-3-( (S)-2-hydroxy-2-phosphonoethyl)oxy-1-N-(phosphonopropionyl)pyrrolidine and [3R,4R-4-guanin-9-yl-3-((S)-2-hydroxy-2-phosphonoethyl)oxy-1-N-(phosphonopropionyl)pyrrolidine (compound 6) are the most potent inhibitors of MtHGPRT yet discovered having K-i values of 60 nM. The crystal structure of the MtHGPRT.6 complex was obtained and compared with that of human HGPRT in complex with the same inhibitor. These structures provide explanations for the 60-fold difference in the inhibition constants between these two enzymes and a foundation for the design of next generation inhibitors. In addition, crystal structures of MtHGPRT in complex with two pyrrolidine nucleoside phosphosphonate inhibitors plus pyrophosphate provide insights into the final stage of the catalytic reaction. As the first step in ascertaining if such compounds have the potential to be developed as anti-TB therapeutics, the tetra-(ethyl L-phenylalanine) tetraamide prodrug of 6 was tested in cell based assays. This compound arrested the growth of virulent Mt not only in its replicating phase (IC50 of 14 mu M) but also in its latent phase (IC50 of 29 mu M). Furthermore, it arrested the growth of Mt in infected macrophages (MIC50 of 85 mu M) and has a low cytotoxicity in mammalian cells (CC50 of 132 +/- 20 mu M). These inhibitors are therefore viewed as forerunners of new anti-TB chemotherapeutics. (C) 2018 Elsevier Masson SAS. All rights reserved.