6-methyl-5-azacytidine | 105330-94-7

• 物质功能分类: 分析化学 - 标准品 - 药典标准品和杂质标准品
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 三嗪类
• 英文名称: 6-methyl-5-azacytidine
• 英文别名: 4-amino-1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-6-methyl-1,3,5-triazin-2-one
• CAS: 105330-94-7
• 化学式: C₉H₁₄N₄O₅
• 分子量: 258.234
• InChiKey: PHHKGVIFQLKTNV-DBRKOABJSA-N

物化性质

• 熔点：
  142-145 °C(Solv: water (7732-18-5); methanol (67-56-1))
• 沸点：
  523.4±60.0 °C(Predicted)
• 密度：
  1.95±0.1 g/cm3(Predicted)
• 溶解度：
  二甲基亚砜：125 mg/mL（484.06 mM）

计算性质

• 辛醇/水分配系数(LogP)：
  -2.2
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  141
• 氢给体数：
  4
• 氢受体数：
  5

制备方法与用途

生物活性

6-Methyl-5-azacytidine 是一种有效的甲基转移酶抑制剂。

反应信息

• 作为产物：
  描述：

  2,3,5-tri-O-benzoyl-β-D-ribosyl isocyanate 在 三甲基氯硅烷 、 sodium methylate 作用下， 以 甲醇 、 三乙胺 、 丙酮 、 乙腈 为溶剂， 反应 24.83h， 生成 6-methyl-5-azacytidine
  参考文献：
  名称：

  6-Methyl-5-Azacytidine-Synthesis, Conformational Properties and Biological Activity. A Comparison of Molecular Conformation with 5-Azacytidine

  摘要：

  The title compound was prepared by the isocyanate procedure and the trimethylsilyl method. The measurement of H-1 NMR spectrum of 6-methyl-5-azacytidine (1) revealed a preference of gamma(t) (46%) rotamer around C(5')-C(4') bond, a predominance of N conformation of the ribose ring (K-eq 0.33) and a preference of syn conformation around the C-N glycosyl bond. An analogous measurement of 5-azacytidine has shown a preference of gamma(+) (60%) rotamer around the C(5')-C(4') bond, a predominance of N conformation of the ribose ring (K-eq 0.41) and a preference of anti conformation around the C-N glycosyl bond. 6-Methyl-5-azacytidine (1) inhibits the growth of bacteria E. coli to the extent of 85% at 4000 mu M concentration and the growth of LoVo/L, a human colon carcinoma cell line, to the extent of 30% at 100 mu M concentration but did not inhibit L1210 cells at less than or equal to 100 mu M concentration. 6-Methyl-5-azacytidine (1) exhibited no in vitro antiviral activity at less than or equal to 1 mu M concentration.

  DOI：

  10.1080/07328319708002528

文献信息

• Synthesis and Antiproliferative Activities of 5-Azacytidine Analogues in Human Leukemia Cells
  作者：Gang Guo、Gang Li、Dan Liu、Qian-Jiao Yang、Yu Liu、Yong-Kui Jing、Lin-Xiang Zhao

  DOI：10.3390/molecules13071487

  日期：——

  Twenty-six 5-azacytidine analogues have been synthesized, including 4-amino- 6-alkyl-1-pyranosyl/ribofuranosyl-1,3,5-triazin-2(1H)-ones 1a-j, 6-amino-4-alkyl/aryl-1- pyranosyl/ribofuranosyl-1,3,5-triazin-2(1H)-ones 2a-f and 4-amino-6-alkyl-1,3,5-triazin-2- yl-1-thio-pyranosides/ribofuranosides 3a-j. The antiproliferative activities of these synthetic analogues were investigated in human leukemia HL-60 cells. Ribofuranosyl Snucleoside 3a, a bioisostere of 5-azacytidine, had a similar antiproliferative ability as that of the latter. Introduction of a methyl at the 6 position of 5-azacytidine and/or replacement of the ribofuranosyl moiety with pyranosyl sugars or disaccharides significantly decreased the antiproliferative activities of the 5-azacytidine derivatives. Several compounds with the replacement of pyranosyl sugars enhanced all-trans retinoic acid-induced differentiation ability in human leukemia HL-60 cells.

  合成了二十六种5-氮杂胞苷类似物，包括4-氨基-6-烷基-1-吡喃糖基/呋喃糖基-1,3,5-三嗪-2(1H)-酮1a-j、6-氨基-4-烷基/芳基-1-吡喃糖基/呋喃糖基-1,3,5-三嗪-2(1H)-酮2a-f和4-氨基-6-烷基-1,3,5-三嗪-2-基-1-硫代吡喃糖基/呋喃糖基3a-j。研究了这些合成类似物在人白血病HL-60细胞中的抗增殖活性。呋喃糖基S核苷3a作为5-氮杂胞苷的生物等排体，具有与后者类似的抗增殖能力。在5-氮杂胞苷的6位引入甲基和/或用吡喃糖基糖或二糖取代呋喃糖基部分显著降低了5-氮杂胞苷衍生物的抗增殖活性。一些用吡喃糖基糖取代的化合物增强了全反式维甲酸诱导的人白血病HL-60细胞的分化能力。
• [EN] SYSTHESIS OF 5-AZACYTIDINE<br/>[FR] SYNTHÈSE DE LA 5-AZACYTIDINE
  申请人：PHARMION LLC

  公开号：WO2012135405A1

  公开（公告）日：2012-10-04

  Provided herein are processes for the preparation of 5-azacytidine, useful for treating, preventing, and/or managing diseases or conditions including cancer, disorders related to abnormal cell proliferation, hematologic disorders, and myelodysplastic syndromes (MDS), wherein 5-azacytidine is represented by the structure:

  本文提供了制备5-azacytidine的过程，用于治疗、预防和/或管理包括癌症、与异常细胞增殖有关的疾病或状况、血液学疾病和骨髓增生异常综合症（MDS）在内的疾病，其中5-azacytidine的结构表示为：
• SYNTHESIS OF 5-AZACYTIDINE
  申请人：Rajendiran Chinnapillai

  公开号：US20140128593A1

  公开（公告）日：2014-05-08

  Provided herein are processes for the preparation of 5-azacytidine, useful for treating, preventing, and/or managing diseases or conditions including cancer, disorders related to abnormal cell proliferation, hematologic disorders, and myelodysplastic syndromes (MDS), wherein 5-azacytidine is represented by the structure:

  本文提供了制备5-氮杂胞苷的方法，可用于治疗、预防和/或管理包括癌症、与异常细胞增殖有关的疾病或病况、血液学疾病和骨髓增生异常综合症（MDS）等疾病或病况，其中5-氮杂胞苷的结构如下：
• 1,3,5-Triazines for Treatment of Viral Diseases
  申请人：Daifuku Richard

  公开号：US20070207973A1

  公开（公告）日：2007-09-06

  The present invention provides compounds and methods for treatment of viral diseases and cancer.

  本发明提供了用于治疗病毒性疾病和癌症的化合物和方法。
• 1,3,5-Triazines for treatment of viral diseases
  申请人：Koronis Pharmaceuticals, Inc.

  公开号：US20040127436A1

  公开（公告）日：2004-07-01

  The present invention provides compounds and methods for treatment of viral diseases and cancer.

  本发明提供了用于治疗病毒性疾病和癌症的化合物和方法。