4-methoxy-5-iodo-7-(β-D-ribofuranosyl)-7H-pyrrolo[2,3-d]pyrimidine | 426823-20-3

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 吡咯并嘧啶核苷和核苷酸
• 英文名称: 4-methoxy-5-iodo-7-(β-D-ribofuranosyl)-7H-pyrrolo[2,3-d]pyrimidine
• 英文别名: 5-iodo-4-methoxy-7-(β-D-ribofuranosyl)-7H-pyrrolo[2,3-d]pyrimidine；4-methoxy-5-iodo-N7-(β-D-ribofuranosyl)-7H-pyrrolo[2,3-d]pyrimidine；(2R,3S,4R,5R)-2-(hydroxymethyl)-5-(5-iodo-4-methoxy-pyrrolo[2,3-d]pyrimidin-7-yl)tetrahydrofuran-3,4-diol；(2R,3S,4R,5R)-2-(hydroxymethyl)-5-(5-iodo-4-methoxypyrrolo[2,3-d]pyrimidin-7-yl)oxolane-3,4-diol
• CAS: 426823-20-3
• 化学式: C₁₂H₁₄IN₃O₅
• 分子量: 407.165
• InChiKey: HPLISFULQJAEBT-WOUKDFQISA-N

物化性质

• 熔点：
  211-212 °C (decomp)(Solv: methanol (67-56-1))
• 沸点：
  646.0±55.0 °C(Predicted)
• 密度：
  2.23±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  110
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  4-methoxy-5-iodo-7-(β-D-ribofuranosyl)-7H-pyrrolo[2,3-d]pyrimidine 在 sodium hydroxide 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 2.0h， 以54%的产率得到3,7-dihydro-5-iodo-7-(β-D-ribofuranosyl)-4H-pyrrolo[2,3-d]pyrimidin-4-one
  参考文献：
  名称：

  C6-O-烷基化的7-脱氮芥子苷核苷类似物：发现有效的和选择性的抗睡眠病药物。

  摘要：

  非洲锥虫病是由原生动物Trypanosoma brucei spp。引起的一种致命的传染病，通过被感染的采采蝇的叮咬传播到新的寄主。目前批准的疗法都有其特定的缺点，促使人们寻找新的治疗剂。T. brucei缺乏从氨基酸前体形成嘌呤环所需的酶，使其依赖于宿主嘌呤的吸收和相互转化。这种依赖性使得嘌呤的类似物和相应的核苷成为潜在的抗-T的有趣来源。布鲁斯代理商。在这项研究中，我们合成和评估了一系列7-取代的7-脱氮芥子碱衍生物，发现6-O-烷基化的类似物特别具有极好的前景，其EC50值在纳摩尔级范围内。SAR对O-烷基链的研究表明，至少在线性烷基链系列中，随着烷基链长度的增加，抗锥虫活性以及细胞毒性也随之增加。然而，这可以通过引入末端分支点来减弱，从而产生高度有效和选择性的类似物36、37和38。无法鉴定出与转运蛋白介导的摄取相关的抗药性，这些类似物中的几种被指定用于进一步的体内跟踪研究。研究。

  DOI：

  10.1016/j.ejmech.2019.112018
• 作为产物：
  描述：

  4-氯-5-碘-7H-吡咯并[2,3-d]嘧啶 在 N,O-双三甲硅基乙酰胺 、 三氟甲磺酸三甲基硅酯 作用下， 以 甲醇 、 乙腈 为溶剂， 反应 3.0h， 生成 4-methoxy-5-iodo-7-(β-D-ribofuranosyl)-7H-pyrrolo[2,3-d]pyrimidine
  参考文献：
  名称：

  C6-O-烷基化的7-脱氮芥子苷核苷类似物：发现有效的和选择性的抗睡眠病药物。

  摘要：

  非洲锥虫病是由原生动物Trypanosoma brucei spp。引起的一种致命的传染病，通过被感染的采采蝇的叮咬传播到新的寄主。目前批准的疗法都有其特定的缺点，促使人们寻找新的治疗剂。T. brucei缺乏从氨基酸前体形成嘌呤环所需的酶，使其依赖于宿主嘌呤的吸收和相互转化。这种依赖性使得嘌呤的类似物和相应的核苷成为潜在的抗-T的有趣来源。布鲁斯代理商。在这项研究中，我们合成和评估了一系列7-取代的7-脱氮芥子碱衍生物，发现6-O-烷基化的类似物特别具有极好的前景，其EC50值在纳摩尔级范围内。SAR对O-烷基链的研究表明，至少在线性烷基链系列中，随着烷基链长度的增加，抗锥虫活性以及细胞毒性也随之增加。然而，这可以通过引入末端分支点来减弱，从而产生高度有效和选择性的类似物36、37和38。无法鉴定出与转运蛋白介导的摄取相关的抗药性，这些类似物中的几种被指定用于进一步的体内跟踪研究。研究。

  DOI：

  10.1016/j.ejmech.2019.112018

文献信息

• 一种贾斯帕霉素的合成方法
  申请人：康化（上海）新药研发有限公司

  公开号：CN112851719A

  公开（公告）日：2021-05-28

  本发明涉及一种贾斯帕霉素的合成方法。主要解决目前合成方法步骤长，成本高的技术问题。本发明合成步骤：4‑氯‑5‑碘‑7H‑吡咯并[2,3‑d]嘧啶和1‑乙酰基‑2,3,5‑三苯甲酰氧基‑1‑beta‑D‑呋喃核糖在N，O‑双（三甲基甲硅烷基）乙酰胺和三氟甲磺酸三甲基硅酯的作用下生成化合物1，产物打浆提纯；化合物1与甲醇钠在甲醇里反应，得到化合物2，无需提纯；化合物2在氢氧化钠水溶液里加热反应生成化合物3，产物打浆提纯；化合物3与氰化亚铜在吡啶里加热反应，所得粗品打浆，重结晶得到目标产物。
• NOVEL SUBSTITUTED 7-DEAZAPURINE RIBONUCLEOSIDES FOR THERAPEUTIC USES
  申请人：Institute of Organic Chemistry and Biochemistry ASCR, v.v.i.

  公开号：US20160159844A1

  公开（公告）日：2016-06-09

  Compounds of Formula I and a pharmaceutically acceptable salt thereof, an optical isomer thereof, or a mixture of optical isomers thereof, as well as compositions which include such compounds and therapeutic methods that utilize such compounds and/or compositions.

  化合物I的盐，其药用上可以接受的盐，其光学异构体或其光学异构体的混合物，以及包括这些化合物的组合物和利用这些化合物和/或组合物的治疗方法。
• 7-Functionalized 7-deazapurine β-d and β-l-ribonucleosides related to tubercidin and 7-deazainosine: glycosylation of pyrrolo[2,3-d]pyrimidines with 1-O-acetyl-2,3,5-tri-O-benzoyl-β-d or β-l-ribofuranose
  作者：Frank Seela、Xin Ming

  DOI：10.1016/j.tet.2007.06.107

  日期：2007.9

  Several 7-functionalized 7-deazapurine ribonucleosides were prepared. Glycosylation of 7-halogenated 6-chloro-7-deazapurines with 1-O-acetyl-2,3,5-tri-O-benzoyl-beta-D-ribofuranose or 1-O-acetyl-2,3,5-tri-O-benzoyl-beta-L-ribofuranose gave the protected beta-D-nucleosides 8c-e (53-62%) and the beta-L-nucleosides 9b-e (57-72%), which were transformed to 7-halogenated 7-deazapurine ribonucleosides related to tubercidin and 7-deazainosine. 7-Alkynyl derivatives (1f,g) and (2f,g) were obtained from the 7-iodo nucleosides 1e and 2e employing the palladium-catalyzed Sonogashira cross-coupling reaction. Within the series of 7-deazaadenosine ( tubercidin) analogues and 7-deazainosine derivatives physical data such as pK(a) values, chromatographic mobilities, C-13 NMR chemical shifts were determined and correlated to each other. (C) 2007 Elsevier Ltd. All rights reserved.
• 6‐Methyl‐7‐Aryl‐7‐Deazapurine Nucleosides as Anti‐ <i>Trypanosoma cruzi</i> Agents: Structure‐Activity Relationship and <i>in vivo</i> Efficacy
  作者：Cai Lin、Ludmila Ferreira de Almeida Fiuza、Camila Cardoso Santos、Daniela Ferreira Nunes、Otacílio Cruz Moreira、Jakob Bouton、Izet Karalic、Louis Maes、Guy Caljon、Fabian Hulpia、Maria Nazaré C. Soeiro、Serge Van Calenbergh

  DOI：10.1002/cmdc.202100144

  日期：2021.7.20

  AbstractChagas disease is a tropical infectious disease resulting in progressive organ‐damage and currently lacks efficient treatment and vaccine options. The causative pathogen, Trypanosoma cruzi, requires uptake and processing of preformed purines from the host because it cannot synthesize these de novo, instigating the evaluation of modified purine nucleosides as potential trypanocides. By modifying the pyrimidine part of a previously identified 7‐aryl‐7‐deazapurine nucleoside, we found that substitution of a 6‐methyl for a 6‐amino group allows retaining T. cruzi amastigote growth inhibitory activity but confers improved selectivity towards mammalian cells. By keeping the 6‐methyl group unaltered, and introducing different 7‐aryl groups, we identified several analogues with sub‐micromolar antitrypanosomal activity. The 7‐(4‐chlorophenyl) analogue 14, which was stable in microsomes, was evaluated in an acute mouse model. Oral administration of 25 mg/kg b.i.d. suppressed peak parasitemia and protected mice from infection‐related mortality, gave similar reductions as the reference drug of blood parasite loads determined by qPCR, but as benznidazole failed to induce sterile cure in the short time period of drug exposure (5 days).
• Study on the Synthesis and PKA-I Binding Activities of 5-Alkynyl Tubercidin Analogues
  作者：Liangren Zhang、Yunlong Zhang、Xianghui Li、Lihe Zhang

  DOI：10.1016/s0968-0896(01)00341-8

  日期：2002.4

  5-Alkynyl tubercidin analogues were synthesized and their biological activities were evaluated. It was found that protein kinase A could be activated by 5-alkynyl tubercidin (9a) and cAMP-binding ability to PKA-I was selectively inhibited by it. Molecular modeling showed that the interaction of 9a and PKA-I was associated with the existence of hydrophobic alkynyl group, During (he synthesis of tubercidin analogues, a pair of 2'-carbonyl participating abnormal coupling products (11a, 11b) was obtained, the structure was identified by X-ray crystalline diffraction. (C). 2002 Elsevier Science Ltd. All rights reserved.