5-iodo-4-methyl-7-(β-D-ribofuranosyl)-7H-pyrrolo[2,3-d]pyrimidine | 1536109-75-7

• 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: 5-iodo-4-methyl-7-(β-D-ribofuranosyl)-7H-pyrrolo[2,3-d]pyrimidine
• 英文别名: (2R,3S,4R,5R)-2-(hydroxymethyl)-5-(5-iodo-4-methyl-pyrrolo[2,3-d]pyrimidin-7-yl)tetrahydrofuran-3,4-diol；(2R,3S,4R,5R)-2-(hydroxymethyl)-5-(5-iodo-4-methylpyrrolo[2,3-d]pyrimidin-7-yl)oxolane-3,4-diol
• CAS: 1536109-75-7
• 化学式: C₁₂H₁₄IN₃O₄
• 分子量: 391.165
• InChiKey: ZMCMFSZUAWKIPE-UGKPPGOTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  101
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  5-iodo-4-methyl-7-(β-D-ribofuranosyl)-7H-pyrrolo[2,3-d]pyrimidine 、 3,4-二氯苯硼酸 在 trisodium tris(3-sulfophenyl)phosphine 、 palladium diacetate 、 sodium carbonate 作用下， 以 水 、 乙腈 为溶剂， 以25%的产率得到4-methyl-5-(3,4-dichloro-phenyl)-N7-(β-D–ribofuranosyl)-7H-pyrrolo[2,3-d]pyrimidine
  参考文献：
  名称：

  6‐Methyl‐7‐Aryl‐7‐Deazapurine Nucleosides as Anti‐ Trypanosoma cruzi Agents: Structure‐Activity Relationship and in vivo Efficacy

  摘要：

  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).

  DOI：

  10.1002/cmdc.202100144
• 作为产物：
  描述：

  4-methyl-7-(β-D-ribofuranosyl)-7H-pyrrolo[2,3-d]pyrimidine 在 N-碘代丁二酰亚胺 、 sodium thiomethoxide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 以58%的产率得到5-iodo-4-methyl-7-(β-D-ribofuranosyl)-7H-pyrrolo[2,3-d]pyrimidine
  参考文献：
  名称：

  NOVEL SUBSTITUTED 7-DEAZAPURINE RIBONUCLEOSIDES FOR THERAPEUTIC USES

  摘要：

  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。

  公开号：

  US20160159844A1

文献信息

• 6-甲基7位脱氮嘌呤核苷类化合物及其用途
  申请人：中国科学院广州生物医药与健康研究院

  公开号：CN107033206B

  公开（公告）日：2020-07-28

  本发明公开了一种6‑甲基7位脱氮嘌呤核苷类化合物及其用途，属于药物化学领域。本发明的具有式I结构特征的6‑甲基7位脱氮嘌呤核苷类化合物或者其药学上可接受的盐，是依据RNA病毒聚合酶的蛋白结构特征，设计和合成的一类新结构的化合物，该类化合物能够抑制RNA病毒，从而可以做为预防和治疗如HCV,流感病毒，HRV(鼻病毒)，RSV，Ebola病毒，登革热病毒以及肠道病毒等RNA病毒感染的潜在药物。
• 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。
• Exploration of 6-methyl-7-(Hetero)Aryl-7-Deazapurine ribonucleosides as antileishmanial agents
  作者：Cai Lin、Izet Karalic、An Matheeussen、Pim-Bart Feijens、Fabian Hulpia、Louis Maes、Guy Caljon、Serge Van Calenbergh

  DOI：10.1016/j.ejmech.2022.114367

  日期：2022.7

  allocated for antileishmanial drug discovery. The Leishmania parasite is deficient in de novo purine synthesis, and therefore acquires purines from the host and processes these using a purine salvage pathway. By making use of purine transport systems and interfering with this salvage pathway, purine (nucleoside) analogues might exert a selective detrimental impact on its growth and survival. In vitro screening

  利什曼病在非洲、亚洲、美洲和南欧的热带和亚热带地区导致高死亡率和高发病率，并以多种临床表现为特征。作为一种被忽视的热带病，有限的资源被分配用于抗寄生虫药物的发现。利什曼原虫缺乏从头合成嘌呤，因此从宿主获取嘌呤并使用嘌呤回收途径进行处理。通过利用嘌呤转运系统并干扰这种补救途径，嘌呤（核苷）类似物可能对其生长和存活产生选择性的有害影响。体外筛选内部嘌呤核苷库和类似物合成提供了 6-methyl-7-(2-pyridyl)-7-deazapurine ribonucleoside 类似物18作为有希望的打击。7-取代基的优化提供了31和32，它们显示出对野生型和抗性L. infantum 、细胞内无鞭毛体和细胞外前鞭毛体形式的有效活性，并且对原代小鼠巨噬细胞 (Mφ) 和 MRC-5 细胞具有良好的选择性。受32良好的体外代谢稳定性的鼓舞，使用早期治疗性L. infantum进行了一项体内研究。仓鼠模型。当以
• US9586986B2
  申请人：——

  公开号：US9586986B2

  公开（公告）日：2017-03-07
• 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).