(2S,3S,4R,5R)-tert-butyl 2-(5-(benzyloxymethyl)-4-methoxy-5H-pyrrolo[3,2-d]pyrimidin-7-yl)-3,4-dihydroxy-5-(hydroxymethyl)pyrrolidine-1-carboxylate | 402477-37-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯并嘧啶类
• 英文名称: (2S,3S,4R,5R)-tert-butyl 2-(5-(benzyloxymethyl)-4-methoxy-5H-pyrrolo[3,2-d]pyrimidin-7-yl)-3,4-dihydroxy-5-(hydroxymethyl)pyrrolidine-1-carboxylate
• 英文别名: (1S)-1-(7-N-benzyloxymethyl-9-deaza-6-O-methylhypoxanthin-9-yl)-N-tert-butoxycarbonyl-1,4-dideoxy-1,4-imino-D-ribitol；tert-butyl (2R,3R,4S,5S)-3,4-dihydroxy-2-(hydroxymethyl)-5-[4-methoxy-5-(phenylmethoxymethyl)pyrrolo[3,2-d]pyrimidin-7-yl]pyrrolidine-1-carboxylate
• CAS: 402477-37-6
• 化学式: C₂₅H₃₂N₄O₇
• 分子量: 500.552
• InChiKey: FJICZUGIYXKHFA-YKWDRNOUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  36
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  139
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  (2S,3S,4R,5R)-tert-butyl 2-(5-(benzyloxymethyl)-4-methoxy-5H-pyrrolo[3,2-d]pyrimidin-7-yl)-3,4-dihydroxy-5-(hydroxymethyl)pyrrolidine-1-carboxylate 在 吡啶 、 4-二甲氨基吡啶 、 1,1'-偶氮(氰基环己烷) 作用下， 以 甲苯 、 乙腈 为溶剂， 反应 28.5h， 生成 2-(5-benzyloxymethyl-4-methoxy-5H-pyrrolo[3,2-d]pyrimidin-7-yl)-5,5,7,7-tetraisopropyl-tetrahydro-4,6,8-trioxa-1-aza-5,7-disila-cyclopentacyclooctene-1-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  Synthesis and Pharmacokinetic and Pharmacodynamic Evaluation of the Forodesine HCl Analog BCX-3040

  摘要：

  Forodesine HCl is a potent inhibitor of the enzyme purine nucleoside phosphorylase (PNP) and is currently in clinical trials for the treatment of leukemia and lymphoma. Animal models indicated that forodesine HCl would have low oral bioavailability in humans and it was initially developed as an intravenous formulation. We were interested in identifying analogs of forodesine HCl with improved oral bioavailability. The 2'-deoxy analog (BCX-3040) was synthesized and its pharmacokinetic and pharmacodynamic properties compared with forodesine HCl.

  DOI：

  10.1080/15257770500267246
• 作为产物：
  描述：

  2,4-二甲基 3-氨基-1H-吡咯-2,4-二羧酸 在 盐酸 、 N-溴代丁二酰亚胺(NBS) 、 正丁基锂 、 水 、 sodium hydride 、 potassium hydroxide 、 三氯氧磷 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 、 乙醇 、 正己烷 、 二氯甲烷 为溶剂， 反应 70.7h， 生成 (2S,3S,4R,5R)-tert-butyl 2-(5-(benzyloxymethyl)-4-methoxy-5H-pyrrolo[3,2-d]pyrimidin-7-yl)-3,4-dihydroxy-5-(hydroxymethyl)pyrrolidine-1-carboxylate
  参考文献：
  名称：

  [EN] ANTIVIRAL AZASUGAR-CONTAINING NUCLEOSIDES
  [FR] NUCLÉOSIDES ANTIVIRAUX CONTENANT DE L'AZASUCRE

  摘要：

  公开号：

  WO2014078778A3

文献信息

• Exploring Structure−Activity Relationships of Transition State Analogues of Human Purine Nucleoside Phosphorylase
  作者：Gary B. Evans、Richard H. Furneaux、Andrzej Lewandowicz、Vern L. Schramm、Peter C. Tyler

  DOI：10.1021/jm030145r

  日期：2003.7.1

  transition state analogue inhibitors of purine nucleoside phosphorylase, a therapeutic target for the control of T-cell proliferation. Immucillin analogues modified at the 2'-, 3'-, or 5'-positions of the azasugar moiety or at the 6-, 7-, or 8-positions of the deazapurine, as well as methylene-bridged analogues, have been synthesized and tested for their inhibition of human purine nucleoside phosphorylase. All

  氮杂-C-核苷Immucillin-H和Immucillin-G是嘌呤核苷磷酸化酶的过渡态类似物抑制剂，嘌呤核苷磷酸化酶是控制T细胞增殖的治疗靶标。已合成在氮杂嘌呤部分的2'-，3'-或5'-位或在脱氮嘌呤的6-，7-或8-位修饰的Immucillin类似物以及亚甲基桥连的类似物。并测试了它们对人嘌呤核苷磷酸化酶的抑制作用。所有类似物都是较弱的抑制剂，这反映了母体imimcillins对过渡状态特征的更好捕获。
• Synthesis of analogs of forodesine HCl, a human purine nucleoside phosphorylase inhibitor—Part II
  作者：Vivekanand P. Kamath、Jie Xue、Jesus J. Juarez-Brambila

  DOI：10.1016/j.bmcl.2009.04.018

  日期：2009.5

  T-cell proliferation. During the filing process for a New Drug Application (NDA) it became evident that there was a need to synthesize some stereo-isomers of forodesine HCl. Herein we present the synthesis of these three novel compounds (2–4).

  盐酸佛丁碱正在研究中，作为控制T细胞增殖的潜在治疗靶标。在新药申请（NDA）的申请过程中，很明显，有必要合成盐酸佛前碱的某些立体异构体。本文我们提出这三种新化合物（合成2 - 4）。
• ANTIVIRAL AZASUGAR-CONTAINING NUCLEOSIDES
  申请人：BIOCRYST PHARMACEUTICALS, INC.

  公开号：US20150291596A1

  公开（公告）日：2015-10-15

  Disclosed are compounds comprising an azasugar attached to a heterocyclic base, including pharmaceutically acceptable salts thereof, suitable for use in inhibiting viral RNA polymerase activity or viral replication, and treating viral infections. The compounds are characterized, in part, by favorable pharmacokinetics for the active pharmaceutical ingredient, particularly in conjunction with enteral administration, including, in particular, oral administration. Also disclosed are pharmaceutical compositions comprising one or more compounds mentioned above, or pharmaceutically acceptable salts thereof, as well as methods for preparing same. Also provided are methods for inhibiting viral RNA polymerase activity, viral replication, and treating viral infections.

  本发明涉及一种含有偶氮糖与杂环碱基结合的化合物，包括其药学上可接受的盐，适用于抑制病毒RNA聚合酶活性或病毒复制，并用于治疗病毒感染。该化合物的特点之一是具有良好的药代动力学，特别是在肠道给药的情况下，包括口服给药。本发明还涉及含有上述一种或多种化合物或其药学上可接受的盐的制药组合物，以及制备它们的方法。本发明还提供了抑制病毒RNA聚合酶活性、病毒复制和治疗病毒感染的方法。