(S)-替加氟 | 55774-30-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 中文名称: (S)-替加氟
• 英文名称: (S)-5-fluoro-1-(tetrahydrofuran-2-yl)pyrimidine-2,4(1H,3H)-dione
• 英文别名: 1-(2-tetrahydrofuryl)-5-fluorouracil；tegafur (α-form)；tegafur；ZINC00016956；(-)-tegafur；Uracil, 5-fluoro-1-(tetrahydro-2-furyl)-, (S)-；5-fluoro-1-[(2S)-oxolan-2-yl]pyrimidine-2,4-dione
• CAS: 55774-30-6
• 化学式: C₈H₉FN₂O₃
• 分子量: 200.169
• InChiKey: WFWLQNSHRPWKFK-LURJTMIESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.3
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  58.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (S)-替加氟 在 glucose-6-phosphate dehydrogenase 、 glucose-6-phosphate 、 CYP₂A_6.1, wild-type 、 烟酰胺腺嘌呤双核苷酸磷酸盐 、 magnesium chloride 作用下， 以 aq. buffer 为溶剂， 生成 5-氟脲嘧啶
  参考文献：
  名称：

  Effect of CYP2A6 Genetic Polymorphism on the Metabolic Conversion of Tegafur to 5-Fluorouracil and Its Enantioselectivity

  摘要：

  替加氟(FT)是一种5-氟尿嘧啶的前体药物,属于手性分子,是R和S两种对映体的消旋混合物,CYP2A6在FT的人源肝微粒体的对映体选择性代谢中发挥重要作用(R-FT>S-FT)。本研究检测了由表达野生型CYP2A6及其编码亚型(CYP2A6*7、*8、*10和*11)的Sf9细胞制备的微粒体对FT的对映体选择性代谢影响。CYP2A6*7、*8、*10和*11是亚洲人群中的高频亚型。同时检测了这些亚型对CYP2A6的探针底物香豆素和尼古丁的代谢水平。酶动力学结果显示,CYP2A6.7(I471T)和CYP2A6.10(I471T和R485L)对FT的R和S对映体的最大反应速率均明显低于野生型酶(CYP2A6.1)及其他亚型,而大多数亚型对FT的R和S对映体的米氏常数均高于CYP2A6.1。对FT的R和S对映体的最大反应速率与米氏常数之比的比值在各亚型间没有明显差异,表明野生型CYP2A6及其亚型对FT的对映体选择性类似,对香豆素7-羟化酶及尼古丁C-氧化酶活性的最大反应速率的影响与对FT的对映体影响有类似趋势,表明CYP2A6亚型中的氨基酸突变导致了酶与底物亲和力的下降,且仅CYP2A6.7和CYP2A6.10的最大反应速率下降。CYP2A6.1及其亚型对FT的R和S对映体的最大反应速率与米氏常数之比的比值相同,表明CYP2A6各亚型中的氨基酸突变对FT的对映体选择性代谢没有影响。

  DOI：

  10.1124/dmd.114.058008
• 作为产物：
  描述：

  (S,E)-5-fluoro-1-(1-(hex-2-enyloxy)allyl)pyrimidine-2,4(1H,3H)-dione 在 Hoveyda-Grubbs catalyst second generation 、 palladium on activated charcoal 、 氢气 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 20.0~40.0 ℃ 、101.33 kPa 条件下， 反应 0.34h， 生成 (S)-替加氟 、 替加氟
  参考文献：
  名称：

  未保护的嘧啶对烷氧基丙二烯的钯催化区域选择性不对称加成反应

  摘要：

  报道了不具有保护和引导基团的N-杂环糖苷的催化不对称合成。关键反应通过未保护的嘧啶的原子效率和区域选择性加成到高度官能化的烷氧基丙二烯上而凸显。获得了许多无环和环状的N-杂环糖苷，而形成的有机副产物却很少。该反应的合成效用通过抗癌药物（-）-替加氟的首次催化不对称合成和氧杂环丁烷核苷衍生物的立体选择性合成得到证明。

  DOI：

  10.1021/acs.orglett.7b02332

文献信息

• SYNTHESIS OF NOVEL OPTICALLY ACTIVE CYCLIC PHOSPHOLIPID CONJUGATES OF TEGAFUR AND URIDINE STARTING FROM L-SERINE
  作者：Zheng-Jie He、Wen-Bin Chen、Cheng-Xiang Zhang、Zheng-Hong Zhou And、Chu-Chi Tang

  DOI：10.1080/10426500008043682

  日期：2000.5.1

  Starting from L-serine, cyclic thiophosphoramidate conjugates (2 and 3) of Tegafur and uridine were synthesized via a multiple-step procedure of esterification, cyclic phosphorylation, and sulfurization, etc. L-serinoate was N-alkylated, then cyclized with phosphorus oxychloride, and further reacted with N-3-(2-hydroxyethyl) Tegafur to afford cyclic phospholipid conjugate 4. The resultants (2, 3, and 4) were successfully separated in the form of pure diastereomer by column chromatography on silica gel. Their configurations were discussed and assigned according to their NMR spectra. The asymmetric induction effects of the carbon-based chiral centre on the diastereomer preference were also observed in these two synthetic phosphorylation cyclizations. The bioassay on their antitumor activities is under investigation.
• USE OF DIANHYDROGALACTITOL OR DERIVATIVES OR ANALOGS THEREOF FOR TREATMENT OF PEDIATRIC CENTRAL NERVOUS SYSTEM MALIGNANCIES
  申请人：DelMar Pharmaceuticals, Inc.

  公开号：US20180071244A1

  公开（公告）日：2018-03-15

  The use of dianhydrogalactitol provides a novel therapeutic modality for the treatment of malignancies of the central nervous system in pediatric patients, including glioblastoma multiforme (GBM) high grade glioma, and medulloblastoma. Dianhydrogalactitol acts as an alkylating agent on DNA that creates N 7 methylation and that can induce double-stranded breaks in DNA. Dianhydrogalactitol is effective in suppressing the growth of cancer stem cells and is active against tumors that are refractory to temozolomide, cisplatin, and tyrosine kinase inhibitors; the drug acts independently of the MGMT repair mechanism. Dianhydrogalactitol can be used together with other anti-neoplastic agents (e.g. cisplatin) and can possess additive or super-additive effects.
• USE OF DIANHYDROGALACTITOL AND DERIVATIVES THEREOF IN THE TREATMENT OF GLIOBLASTOMA, LUNG CANCER, AND OVARIAN CANCER
  申请人：Bacha Jeffrey A.

  公开号：US20190091195A1

  公开（公告）日：2019-03-28

  Substituted hexitol derivatives such as dianhydrogalactitol are useful in the treatment of various neoplastic pathologies. Said pathologies include glioblastoma multiforme, non-small-cell lung carcinoma (NSCLC), ovarian cancer, and leptomeningeal carcinomatosis. The anti-neoplastic activity of dianhydrogalactitol is demonstrated to be due to its activity as an alkylating agent that creates N 7 methylation and inter-strand DNA crosslinks. The hexitol derivatives may be used alone or in combination with other anti-neoplastic agents.
• US4169201A
  申请人：——

  公开号：US4169201A

  公开（公告）日：1979-09-25
• US5457187A
  申请人：——

  公开号：US5457187A

  公开（公告）日：1995-10-10