5'-O-(4-monomethoxytrityl)-2'-deoxy-5-fluorouridine | 103767-37-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: 5'-O-(4-monomethoxytrityl)-2'-deoxy-5-fluorouridine
• 英文别名: 5'-O-(4-monomethoxytrityl)-5-fluoro-2'-deoxyuridine；2'-deoxy-5-fluoro-5'-O-(monomethoxytrityl)uridine；5'-O-(monomethoxytrityl)-5-fluoro-2'-deoxyuridine；2'-deoxy-5-fluoro-5'-O-(4-methoxytrityl)uridine；5-fluoro-1-[(2R,4S,5R)-4-hydroxy-5-[[(4-methoxyphenyl)-diphenylmethoxy]methyl]oxolan-2-yl]pyrimidine-2,4-dione
• CAS: 103767-37-9
• 化学式: C₂₉H₂₇FN₂O₆
• 分子量: 518.542
• InChiKey: PRAWNTJUUJADEN-JIMJEQGWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  38
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  97.3
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  5'-O-(4-monomethoxytrityl)-2'-deoxy-5-fluorouridine 在 吡啶 、 溶剂黄146 作用下， 反应 4.33h， 生成 β-5-Fluor-3'-acetyl-2'-desoxy-uridin
  参考文献：
  名称：

  Synthesis and Biological Activity of Aromatic Amino Acid Phosphoramidates of 5-Fluoro-2‘-deoxyuridine and 1-β-Arabinofuranosylcytosine:  Evidence of Phosphoramidase Activity

  摘要：

  The amino acid phosphoramidate diesters of FUdR (2) and Ara-C (6), 5-fluoro-2'-deoxy-5'-uridyl N-(1-carbomethoxy-2-phenylethyl)phosphor (5a), 5-fluoro-2'-deoxy-5'-uridyl N-(1-carbomethoxy-2-indolylethyl)phosphoramidate (5b), 1-beta-arabinofuranosylcytosine 5'-N-(1-carbomethoxy-2-phenylethyl)phosphoramidate (8a), and 1-beta-arabinofuranosylcytosine 5'-N-(1-carbomethoxy-2-indolylethyl)phosphoramidate (8b), were synthesized and tested for their antitumor activity against L1210 mouse lymphocytic leukemia cells and CCRF-CEM human T-cell lymphoblastic leukemia cells. Ara-C phosphoramidates 8a,b were found to be inactive at a concentration of 100 mu M, while the FUdR conjugates 5a,b exhibited IC50 values within a range of 0.30-0.40 mu M. Stability studies revealed that >99% of the phosphoramidates remained intact after incubation for >2 days in 20% calf or 20% human serum. Intracellular thymidylate synthase (TS) inhibition studies revealed that treatment of L1210 and CCRF-CEM cells with 5a or 5b resulted in significant inhibition of TS in intact and permeabilized cells, while treatment of L929 TK- cells with these compounds did not result in inhibition of TS activity in intact cells. However, permeabilization of L929 TK- cells enhanced the activity of 5a,b toward intracellular TS by 900- and 1500-fold, respectively. In addition, incubation of cell-free extracts of CEM cells with radiolabeled 5b resulted in the rapid production of FUdR 5'-monophosphate and a lag in the generation of FUdR. Consequently, it is proposed that the metabolism of the phosphoramidate diesters of FUdR in proliferating tissue proceeds through two separate enzymatic steps involving P-N bond cleavage by an unknown phosphoramidase followed by P-O bond cleavage by phosphatases such as 5'-nucleotidase.

  DOI：

  10.1021/jm9603680
• 作为产物：
  描述：

  4-甲氧基三苯基氯甲烷 、 5-氟-2'-脱氧脲核苷 以 吡啶 为溶剂， 反应 24.0h， 以86%的产率得到5'-O-(4-monomethoxytrityl)-2'-deoxy-5-fluorouridine
  参考文献：
  名称：

  核苷酸。部分。XXXII。2'–5'连接寡核苷酸的合成。抗病毒和抗肿瘤核苷的前药†

  摘要：

  具有细胞毒性和抗病毒活性的化合物bvU d（1），flU d（4），阿昔洛韦（7）和A a（12）已通过磷酸三酯法与适当保护的（2'-5'）二聚腺苷酸20化学结合给予2'-5'核苷酸三聚体21 - 24。通过化学方法的各种保护基团，得到的脱保护的2'-5'三聚体25 - 28，这可以看作是一种新型的潜在前药形式，可将核苷酸传递至细胞内的靶标。在一系列类似的反应中，将9-（3'-叠氮基3'-脱氧-β-D-木呋喃糖基）腺嘌呤与7偶联到2'-5'三聚体31上。对寡核苷酸25-27和31的抗病毒筛选显示出与亲本核苷密切相关的生物学活性，可能表明它们是通过酶切低聚物而释放的。

  DOI：

  10.1002/hlca.19890720811

文献信息

• ETHYNYLATED HETERODINUCLEOSIDE PHOSPHATE ANALOGS, METHOD FOR THE PRODUCTION THEREOF, AND USE THEREOF
  申请人：Schott Herbert

  公开号：US20100151001A1

  公开（公告）日：2010-06-17

  The invention relates to novel ethynylated heterodinucleoside phosphate analogs, the production thereof, substances containing at least one of said compounds, and the use thereof for the treatment of cancer and infectious diseases.

  该发明涉及新颖的乙炔基杂二核苷酸磷酸盐类似物，其生产，含有至少一种该化合物的物质，以及将其用于治疗癌症和传染病。
• Synthesis and anticancer activities of amphiphilic 5-fluoro-2′-deoxyuridylic acid prodrugs
  作者：Peter S. Ludwig、Reto A. Schwendener、Herbert Schott

  DOI：10.1016/j.ejmech.2004.12.006

  日期：2005.5

  lyl-(3' --> 5')-3'-O-acetyl-5-fluoro-2'-deoxyuridine (dC(pam)-5-FdU(Ac), N4-palmitoyl-2',3'-dideoxycytidylyl-(5' --> 5')-3'-O-acetyl-5-fluoro-2'-deoxyuridine (ddC(pam)-(5' --> 5')-5-FdU(Ac), 5-fluoro-2'-deoxyuridylyl-(3' --> 5')-5-fluoro-N4-hexadecyl-2'-deoxycytidine (5-FdU-5-FdC(hex)), and of the new liponucleotide 1-O-octadecyl-rac-glycerylyl-(3 --> 5')-5-fluoro-2'-deoxyuridine (Oct1Gro-(3 --> 5')-5-FdU)

  5'-氟-2'-脱氧尿苷-5'-单磷酸酯（5-FdUMP）的两亲抗癌前药是通过将亲脂性胞嘧啶衍生物或磷脂与5-氟-2'-脱氧尿苷偶联的氢膦酸盐方法合成的（5 -FdU）。美国国家癌症研究所体外抗癌筛选计划内的研究表明，异二核苷磷酸酯具有很高的抗癌活性：N4-棕榈酰基-2'-脱氧胞嘧啶-（3'-> 5'）-3'-O-乙酰基-5 -氟-2'-脱氧尿苷（dC（pam）-5-FdU（Ac），N4-棕榈酰基-2'，3'-二脱氧胞嘧啶-（5'-> 5'）-3'-O-乙酰基-5 -氟-2'-脱氧尿苷（ddC（pam）-（5'-> 5'）-5-FdU（Ac），5-氟-2'-脱氧尿苷-（3'-> 5'）-5 -氟-N4-十六烷基-2'-脱氧胞苷（5-FdU-5-FdC（hex）），以及新的脂核苷酸1-O-十八烷基-rac-甘油基-（3-> 5'）-5-氟-2'-脱氧尿苷（Oct1Gro-（3-> 5'）-5
• Synthesis and in vitro activities of new anticancer duplex drugs linking 2′-deoxy-5-fluorouridine (5-FdU) with 3′-C-ethynylcytidine (ECyd) via a phosphodiester bonding
  作者：Herbert Schott、Sarah Schott、Reto A. Schwendener

  DOI：10.1016/j.bmc.2009.08.033

  日期：2009.10

  Two isomeric cytostatic duplex drugs 2'-deoxy-5-fluorouridylyl-(3'-> 5')-3'-C-ethynylcytidine [5-FdU(3'-> 5')ECyd] and 2'-deoxy-5-fluorouridylyl-(5'-> 5')-3'-C-ethynylcytidine [5-FdU(5'-> 5')ECyd] were designed and synthesized at gram scale according to the hydrogenphosphonate method in an overall yield of about 40%. The in vitro evaluation of the anticancer effects indicated highly varying sensibilities of the panel of 60 tested tumor cell lines against the duplex drugs. 5-FdU(3'-> 5')ECyd had a 50% growth inhibition (IC50 <= 10 (8) M) in 44/58 cell lines. However, only 25/53 of those cell lines showed corresponding IC50 values when the isomeric 5-FdU(5'-> 5')ECyd was tested. Total growth inhibition was achieved using micromolar concentrations of the duplex drugs. The 5-FdU residue of the duplex drug can cause very different effects like additive, synergistic, antagonistic as well as sequence-depending activities, which drastically changed efficiency as well as specificity of the anticancer activities of the duplex drugs, in comparison to those of the monomeric drugs. (C) 2009 Elsevier Ltd. All rights reserved.
• HERDEWIJN, PIET;CHARUBALA, RAMAMURTHY;DE, CLEREQ ERIK;PFLEIDERER, WOLFGAN+, HELV. CHIM. ACTA, 72,(1989) N, C. 1739-1748
  作者：HERDEWIJN, PIET、CHARUBALA, RAMAMURTHY、DE, CLEREQ ERIK、PFLEIDERER, WOLFGAN+

  DOI：——

  日期：——
• 5-FLUOROURACIL DERIVATIVES
  申请人：THE WELLCOME FOUNDATION LIMITED

  公开号：EP0726904A1

  公开（公告）日：1996-08-21