5-Azacitidine | 65886-71-7

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 5-Azacitidine
• 英文别名: 5-azacytidine；Azacitidine；Azacytidine, 5-；4-amino-1-[3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-1,3,5-triazin-2-one
• CAS: 65886-71-7
• 化学式: C₈H₁₂N₄O₅
• 分子量: 244.207
• InChiKey: NMUSYJAQQFHJEW-UHFFFAOYSA-N

物化性质

• 熔点：
  220 °C (decomp)
• 沸点：
  534.5±60.0 °C(Predicted)
• 密度：
  2.08±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -2.2
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  141
• 氢给体数：
  4
• 氢受体数：
  5

ADMET

毒理性

• 在妊娠和哺乳期间的影响

◉ 母乳喂养期间使用总结：大多数来源认为，在母亲抗肿瘤药物治疗期间，母乳喂养是禁忌的。在间歇性阿扎胞苷治疗期间，可能可以在适当的母乳禁食期后安全地进行母乳喂养；制造商建议在最后一剂后的禁食期为1周。化疗可能会不利地影响母乳的正常微生物组和化学成分。[1] 在怀孕期间接受化疗的妇女更可能在哺乳婴儿时遇到困难。[2] ◉ 对母乳喂养婴儿的影响：截至修订日期，未找到相关已发布信息。 ◉ 对泌乳和母乳的影响：对74名在怀孕第二或第三季度在一个中心接受癌症化疗的妇女进行了电话随访研究，以确定她们产后是否成功进行母乳喂养。只有34%的妇女能够专门母乳喂养她们的婴儿，而66%的妇女报告遇到母乳喂养困难。这与其他22位在怀孕期间被诊断但未接受化疗的母亲91%的母乳喂养成功率形成了对比。其他具有统计学意义的相关性包括：1. 有母乳喂养困难的母亲平均接受了5.5个周期的化疗，而没有困难的母亲平均接受了3.8个周期；2. 有母乳喂养困难的母亲在怀孕期间平均提前3.4周接受了第一次化疗周期。在接受含有氟尿嘧啶方案治疗的9名妇女中，有8名遇到母乳喂养困难。[2]

◉ Summary of Use during Lactation:Most sources consider breastfeeding to be contraindicated during maternal antineoplastic drug therapy. It might be possible to breastfeed safely during intermittent azacitidine therapy with an appropriate period of breastfeeding abstinence; the manufacturer recommends an abstinence period of 1 week after the last dose. Chemotherapy may adversely affect the normal microbiome and chemical makeup of breastmilk.[1] Women who receive chemotherapy during pregnancy are more likely to have difficulty nursing their infant.[2] ◉ Effects in Breastfed Infants:Relevant published information was not found as of the revision date. ◉ Effects on Lactation and Breastmilk:A telephone follow-up study was conducted on 74 women who received cancer chemotherapy at one center during the second or third trimester of pregnancy to determine if they were successful at breastfeeding postpartum. Only 34% of the women were able to exclusively breastfeed their infants, and 66% of the women reported experiencing breastfeeding difficulties. This was in comparison to a 91% breastfeeding success rate in 22 other mothers diagnosed during pregnancy, but not treated with chemotherapy. Other statistically significant correlations included: 1. mothers with breastfeeding difficulties had an average of 5.5 cycles of chemotherapy compared with 3.8 cycles among mothers who had no difficulties; and 2. mothers with breastfeeding difficulties received their first cycle of chemotherapy on average 3.4 weeks earlier in pregnancy. Of the 9 women who received a fluorouracil-containing regimen, 8 had breastfeeding difficulties.[2]

来源:Drugs and Lactation Database (LactMed)

文献信息

• POLYMER PARTICLES OR NANO-VECTORS AND USE THEREOF AS A DRUG AND/OR DIAGNOSTIC AGENT
  申请人：Bertrand Philippe

  公开号：US20140219925A1

  公开（公告）日：2014-08-07

  Novel polymer nanovectors or particles and use thereof as medication and/or diagnostic agents.

  新型聚合物纳米载体或颗粒及其作为药物和/或诊断试剂的用途。
• [EN] COMBINATION THERAPIES FOR TREATMENT OF MYELODYSPLASTIC SYNDROME<br/>[FR] POLYTHÉRAPIES POUR LE TRAITEMENT DU SYNDROME MYÉLODYSPLASIQUE
  申请人：SUMITOMO DAINIPPON PHARMA ONCOLOGY INC

  公开号：WO2021113688A1

  公开（公告）日：2021-06-10

  The present invention relates to methods for treatment of myelodysplastic syndrome (MDS) by administration of a hypomethylating agent (HMA), such as azacitidine or decitabine, or a prodrug of either of the foregoing, or a pharmaceutically acceptable salt of any of the foregoing, and alvocidib, or a prodrug thereof, or a pharmaceutically acceptable salt of the foregoing.

  本发明涉及通过给予低甲基化剂（HMA），如氮芥胺或地西他滨，或者以上述任一药物的前体或药学上可接受的任何盐，以及阿沃西地（alvocidib），或者其前体，或者上述药物的药学上可接受的任何盐，来治疗骨髓增生异常综合征（MDS）的方法。
• [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：
• ANTIPROLIFERATIVE COMPOUNDS AND SECOND ACTIVE AGENTS FOR COMBINED USE
  申请人：Celgene Corporation

  公开号：US20200215060A1

  公开（公告）日：2020-07-09

  Provided herein are methods of using 4-(4-(4-(((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)oxy)methyl)benzyl)piperazin-1-yl)-3-fluorobenzonitrile, or an enantiomer, a mixture of enantiomers, a tautomer, or a pharmaceutically acceptable salt thereof, in combination with a second active agent for treating, preventing or managing multiple myeloma. The second active agent is one or more of a BTK inhibitor, an mTOR inhibitor, a PIM inhibitor, an IGF-1R inhibitor, an MEK inhibitor, an XPO1 inhibitor, a DOT1L inhibitor, an EZH2 inhibitor, a JAK2 inhibitor, a BRD4 inhibitor, a PLK 1 inhibitor, an NEK2 inhibitor, an AURKB inhibitor, a BIRC5 inhibitor, a BET inhibitor, or a DNA methyltransferase inhibitor.

  本文提供了使用4-(4-(4-(((2-(2,6-二氧代哌啶-3-基)-1-氧代异吲哚啉-4-基)氧基)甲基)苄基)哌嗪-1-基)-3-氟苯甲腈，或其对映体、对映体混合物、互变异构体或其药学上可接受的盐，与第二活性剂结合用于治疗、预防或管理多发性骨髓瘤的方法。第二活性剂是BTK抑制剂、mTOR抑制剂、PIM抑制剂、IGF-1R抑制剂、MEK抑制剂、XPO1抑制剂、DOT1L抑制剂、EZH2抑制剂、JAK2抑制剂、BRD4抑制剂、PLK1抑制剂、NEK2抑制剂、AURKB抑制剂、BIRC5抑制剂、BET抑制剂或DNA甲基转移酶抑制剂中的一个或多个。
• PROCESS FOR THE SYNTHESIS OF AZACITIDINE AND DECITABINE
  申请人：DE FERRA Lorenzo

  公开号：US20110245485A1

  公开（公告）日：2011-10-06

  Described herein is a process for the synthesis of azacitidine or decitabine, comprising the silylation of azacytosine in the presence of N,O-bis-trimethylsilyl-trifluoroacetamide. Such reaction is performed in an organic solvent, preferably aprotic, even more preferably selected from among dichloromethane, dichloroethane and/or acetonitrile. According to a further aspect of the process, 2 to 3 moles of N,O-bis-trimethylsilyl-trifluoroacetamide are used per mole of azacytosine, preferably from 2.2 to 2.5.

  本文描述了一种合成氮杂胞嘧啶或脱氧胞苷的过程，其中包括在N,O-双(三甲基硅基)三氟乙酰胺的存在下对氮杂胞嘧啶进行硅化反应。该反应在有机溶剂中进行，最好是无极性的，更好的是选择二氯甲烷、二氯乙烷和/或乙腈。根据该过程的另一个方面，每摩尔氮杂胞嘧啶使用2至3摩尔N,O-双(三甲基硅基)三氟乙酰胺，最好是从2.2到2.5。