(2S)-N-(tert-butyloxycarbonyl)-2-(dibenzylphosphoxymethyl)pyrrolidine | 615583-02-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: (2S)-N-(tert-butyloxycarbonyl)-2-(dibenzylphosphoxymethyl)pyrrolidine
• 英文别名: (S)-tert-butyl 2-(((bis(benzyloxy)phosphoryl)oxy)methyl)pyrrolidine-1-carboxylate；dibenzyl (S)-N-Boc-2-hydroxymethyl-pyrrolidinyl monophosphate；tert-butyl (2S)-2-[bis(phenylmethoxy)phosphoryloxymethyl]pyrrolidine-1-carboxylate
• CAS: 615583-02-3
• 化学式: C₂₄H₃₂NO₆P
• 分子量: 461.495
• InChiKey: HIQWDUACAIEXDZ-QFIPXVFZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.94
• 重原子数：
  32.0
• 可旋转键数：
  9.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  74.3
• 氢给体数：
  0.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  (2S)-N-(tert-butyloxycarbonyl)-2-(dibenzylphosphoxymethyl)pyrrolidine 在 palladium on activated charcoal 氢气 作用下， 以 甲醇 为溶剂， 反应 16.0h， 以100%的产率得到(2S)-N-(tert-butyloxycarbonyl)-2-(phosphoxymethyl)pyrrolidine
  参考文献：
  名称：

  SAR Analysis of Adenosine Diphosphate (Hydroxymethyl)pyrrolidinediol Inhibition of Poly(ADP-ribose) Glycohydrolase

  摘要：

  Polyadenosine diphosphoribose glycohydrolase (PARG) catalyzes the intracellular hydrolysis of adenosine diphosphoribose polymers. Because structure-activity data are lacking for PARG, the specific inhibitor adenosine diphosphate (hydroxymethyl)pyrrolidinediol (ADP-HPD) was utilized to determine the effects of structure on inhibitor potency using PARG isolated from bovine thymus (bPARG) and recombinant bovine PARG catalytic fragment (rPARG-CF). Both enzymes were strongly inhibited by submicromolar levels of ADP-HPD, but ADP and the phosphorylated pyrrolidine displayed no activity. Utilizing ADP-HPD analogues containing 2-, N-6, or 8-adenosyl substituents or guanine instead of adenine, the importance of adenine ring recognition as well as a correlation between loss of PARG inhibition and the length and bulkiness of 8-adenosyl substituents was shown. Utilization of ADP-HPD analogues lacking one or both pyrrolidine cis-hydroxyls demonstrated their importance for inhibitor binding. Last, the similarity between naturally occurring bPARG and heterologously expressed rPARG-CF was demonstrated. Therefore, readily available rPARG-CF is suitable for use in future studies to determine the structural aspects of PARG.

  DOI：

  10.1021/jm020541u
• 作为产物：
  描述：

  Boc-L-脯氨酸甲酯 在 四氮唑 、 锂硼氢 、 间氯过氧苯甲酸 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 8.0h， 生成 (2S)-N-(tert-butyloxycarbonyl)-2-(dibenzylphosphoxymethyl)pyrrolidine
  参考文献：
  名称：

  SAR Analysis of Adenosine Diphosphate (Hydroxymethyl)pyrrolidinediol Inhibition of Poly(ADP-ribose) Glycohydrolase

  摘要：

  Polyadenosine diphosphoribose glycohydrolase (PARG) catalyzes the intracellular hydrolysis of adenosine diphosphoribose polymers. Because structure-activity data are lacking for PARG, the specific inhibitor adenosine diphosphate (hydroxymethyl)pyrrolidinediol (ADP-HPD) was utilized to determine the effects of structure on inhibitor potency using PARG isolated from bovine thymus (bPARG) and recombinant bovine PARG catalytic fragment (rPARG-CF). Both enzymes were strongly inhibited by submicromolar levels of ADP-HPD, but ADP and the phosphorylated pyrrolidine displayed no activity. Utilizing ADP-HPD analogues containing 2-, N-6, or 8-adenosyl substituents or guanine instead of adenine, the importance of adenine ring recognition as well as a correlation between loss of PARG inhibition and the length and bulkiness of 8-adenosyl substituents was shown. Utilization of ADP-HPD analogues lacking one or both pyrrolidine cis-hydroxyls demonstrated their importance for inhibitor binding. Last, the similarity between naturally occurring bPARG and heterologously expressed rPARG-CF was demonstrated. Therefore, readily available rPARG-CF is suitable for use in future studies to determine the structural aspects of PARG.

  DOI：

  10.1021/jm020541u

文献信息

• [EN] INHIBITORS OF INDOLEAMINE 2,3-DIOXYGENASE AND METHODS OF THEIR USE<br/>[FR] INHIBITEURS D'INDOLÉAMINE 2,3-DIOXYGÉNASE ET LEURS PROCÉDÉS D'UTILISATION
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2019136112A1

  公开（公告）日：2019-07-11

  The present invention provides a compound of formula (II): an inhibitor of indoleamine 2,3-dioxygenase (IDO), which may be used as medicaments for the treatment of proliferative disorders, such as cancer, viral infections and/or autoimmune diseases. Its prodrugs are disclosed.

  本发明提供了一种化合物，其化学式为(II)：一种吲哌酮胺2,3-二氧化酶（IDO）抑制剂，可用作治疗增生性疾病，如癌症、病毒感染和/或自身免疫疾病的药物。其前药也已被披露。
• Diphosphate formation using cyanuric chloride or triisopropylbenzenesulfonyl chloride as the activating agents
  作者：Teng-Chi Lin、Jim-Min Fang

  DOI：10.1016/j.tetlet.2011.01.034

  日期：2011.4

  By using cyanuric chloride or 2,4,6-triisopropylbenzenesulfonyl chloride (TIPSCl) as the condensing agent and magnesium bromide as the promoter, the phosphate cross-coupling reactions are effectively carried out to give lipid-saccharide and pyrrolidine-guanosine diphosphates. Under optimized conditions, the TIPSCl-facilitated cross-coupling reactions complete in a short reaction time (similar to 5 h) without the complication of possible self-coupling reactions. (c) 2011 Elsevier Ltd. All rights reserved.
• INHIBITORS OF INDOLEAMINE 2,3-DIOXYGENASE AND METHODS OF THEIR USE
  申请人：BRISTOL-MYERS SQUIBB COMPANY

  公开号：US20210070698A1

  公开（公告）日：2021-03-11

  The present invention provides a compound of formula (II): an inhibitor of indoleamine 2,3-dioxygenase (IDO), which may be used as medicaments for the treatment of proliferative disorders, such as cancer, viral infections and/or autoimmune diseases. Its prodrugs are disclosed.