5-(3-fluoropropyn-1-yl)-2'-deoxyuridine | 267007-11-4

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷
• 英文名称: 5-(3-fluoropropyn-1-yl)-2'-deoxyuridine
• 英文别名: 5-(3-fluoroprop-1-ynyl)-1-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidine-2,4-dione
• CAS: 267007-11-4
• 化学式: C₁₂H₁₃FN₂O₅
• 分子量: 284.244
• InChiKey: UGTHKKWHIIZHSU-IVZWLZJFSA-N

物化性质

• 密度：
  1.56±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  99.1
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  5-(3-fluoropropyn-1-yl)-2'-deoxyuridine 在 吡啶 、 磷酸三乙酯 、 水 、 三氯氧磷 作用下， 反应 5.0h， 生成 5-fluoropropynyl-2'-deoxyuridine 5'-phosphate
  参考文献：
  名称：

  5-（3-氟丙炔-1-基）-2'-脱氧尿苷5'-磷酸基于机理的胸苷酸合酶失活。

  摘要：

  5-氟丙炔基-2'-脱氧尿苷5'-磷酸（3）被设计为基于机制的胸苷酸合酶（TS）失活剂。通过钯催化的偶联，由5-碘-2'-脱氧尿苷和炔丙醇合成抑制剂，然后进行氟化和选择性磷酸化。在存在或不存在CH2H4叶酸辅因子的情况下，将TS与3一起孵育会导致酶快速，不可逆地失活。

  DOI：

  10.1016/s0960-894x(00)00012-3
• 作为产物：
  描述：

  3',5'-双乙酰基-5-碘-脱氧尿苷 在 盐酸 、 甲醇 、 copper(l) iodide 、 四(三苯基膦)钯 、 三乙胺 、 4,4'-二氨基二苯乙烯-2,2'-二磺酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 22.0h， 生成 5-(3-fluoropropyn-1-yl)-2'-deoxyuridine
  参考文献：
  名称：

  5-（3-氟丙炔-1-基）-2'-脱氧尿苷5'-磷酸基于机理的胸苷酸合酶失活。

  摘要：

  5-氟丙炔基-2'-脱氧尿苷5'-磷酸（3）被设计为基于机制的胸苷酸合酶（TS）失活剂。通过钯催化的偶联，由5-碘-2'-脱氧尿苷和炔丙醇合成抑制剂，然后进行氟化和选择性磷酸化。在存在或不存在CH2H4叶酸辅因子的情况下，将TS与3一起孵育会导致酶快速，不可逆地失活。

  DOI：

  10.1016/s0960-894x(00)00012-3

文献信息

• Rational Design of Selective Antimetabolites of DNA-Thymine Biosynthesis: 5-Propynylpyrimidine Nucleoside Derivatives
  作者：Thomas I. Kalman、Zhe Nie

  DOI：10.1080/15257770008033014

  日期：2000.1

  A novel series of 5-propynylpyrimidine nucleosides are proposed as potential antimetabolites of DNA-thymine biosynthesis. This proposal is based on the results of detailed mechanistic analyses of the molecular interactions between dTMP synthase and its inhibitors. It is proposed that a propynyl side-chain at the 5-position of dUMP, bearing an appropriate leaving group, would cause irreversible inactivation

  提出了一系列新的5-丙炔基嘧啶核苷作为DNA-胸腺嘧啶生物合成的潜在抗代谢物。该提议基于对dTMP合酶与其抑制剂之间分子相互作用的详细机理分析的结果。建议在带有适当离去基团的dUMP的5位丙炔基侧链会引起dTMP合酶的不可逆失活，而这不需要辅因子CH2H4叶酸的存在。
• Selective cellular targeting: multifunctional delivery vehicles, multifunctional prodrugs, use as antineoplastic drugs
  申请人：Drug Innovation & Design, Inc.

  公开号：US20030138432A1

  公开（公告）日：2003-07-24

  The present invention relates to the compositions, methods, and applications of a novel approach to selective cellular targeting. The purpose of this invention is to enable the selective delivery and/or selective activation of effector molecules to target cells for diagnostic or therapeutic purposes. The present invention relates to multi-functional prodrugs or targeting vehicles wherein each functionality is capable of enhancing targeting selectivity, affinity, intracellular transport, activation or detoxification. The present invention also relates to ultra-low dose, multiple target, multiple drug chemotherapy and targeted immunotherapy for cancer treatment.

  本发明涉及一种新的选择性细胞靶向的组合物、方法和应用。本发明的目的是为了实现对目标细胞的选择性输送和/或选择性激活效应分子，以进行诊断或治疗。本发明涉及多功能前药或靶向载体，其中每个功能都能增强靶向选择性、亲和力、细胞内转运、激活或解毒。本发明还涉及超低剂量、多靶点、多药物化疗和靶向免疫疗法，用于癌症治疗。
• SELECTIVE CELLULAR TARGETING: MULTIFUNCTIONAL DELIVERY VEHICLES
  申请人：Drug Innovation & Design, Inc.

  公开号：EP1255567A1

  公开（公告）日：2002-11-13
• [EN] 5-PROPYNYLPYRIMIDINE DERIVATIVES AS CYTOTOXIC ENZYME INHIBITORS<br/>[FR] DERIVES 5-PROPYNYLPYRIMIDINE UTILISES COMME INHIBITEURS D'ENZYME CYTOTOXIQUE
  申请人：UNIV NEW YORK STATE RES FOUND

  公开号：WO2001014345A1

  公开（公告）日：2001-03-01

  Disclosed are 5-propynylpyrimidine derivatives of formula (I) wherein X is a leaving group, R1 is selected from the group consisting of -OH,-NH2, and -SH; R2 is selected from the group consisting of -H, 2-deoxyribose and ester derivatives thereof. Also disclosed is a method for the synthesis of the 5-propynylpyrimidines. These compounds are useful as cytotoxic agents.
• [EN] SELECTIVE CELLULAR TARGETING: MULTIFUNCTIONAL DELIVERY VEHICLES<br/>[FR] CIBLAGE CELLULAIRE SELECTIF: VECTEURS D'ADMINISTRATION MULTIFONCTIONNELS
  申请人：DRUG INNOVATION & DESIGN INC

  公开号：WO2001036003A2

  公开（公告）日：2001-05-25

  The present invention relates to the compositions, methods, and applications of a novel approach to selective cellular targeting. The purpose of this invention is to enable the selective delivery and/or selective activation of effector molecules to target cells for diagnostic or therapeutic purposes. The present invention relates to multi-functional prodrugs or targeting vehicles wherein each functionality is capable of enhancing targeting selectivity, affinity, intracellular transport, activation or detoxification. The present invention also relates to ultralow dose, multiple target, multiple drug chemotherapy and targeted immunotherapy for cancer treatment.