5-pent-1-ynyluracil | 1174912-51-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 5-pent-1-ynyluracil
• 英文别名: 5-pentynyl-uracil；5-pent-1-ynyl-1H-pyrimidine-2,4-dione
• CAS: 1174912-51-6
• 化学式: C₉H₁₀N₂O₂
• 分子量: 178.191
• InChiKey: NIOWRPKKLZMTPC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  58.2
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  5-pent-1-ynyluracil 在 copper(l) iodide 、 三乙胺 作用下， 以 甲醇 为溶剂， 反应 3.0h， 以50%的产率得到6-propyl-2,3-dihydrofuro[2,3-d]pyrimidin-2-one
  参考文献：
  名称：

  Inhibition of Mycobacterial Replication by Pyrimidines Possessing Various C-5 Functionalities and Related 2′-Deoxynucleoside Analogues Using in Vitro and in Vivo Models

  摘要：

  Tuberculosis (TB) has become an increasing problem since the emergence of human immunodeficiency virus and increasing appearance of drug-resistant strains. There is an urgent need to advance our knowledge and discover a new class of agents that are distinct than current therapies. Antimycobacterial activities of several 5-alkyl, 5-alkynyl, furanopyrimiclines and related 2'-deoxynucleosides were investigated against Mycobacterium tuberculosis. Compounds with 5-arylalkynyl substituents (23-26,33, 35) displayed potent in vitro antitubercular activity against Mycobacterium bovis and Mycobacterium tuberculosis. The in vivo activity of 5-(2-pyridylethyny1)-uracil (26) and its 2'-deoxycytidine analogue, 5-(2-pyridylethynyI)-2'-deoxycytidine (35), was assessed in BA LB/c mice infected with M. tuberculosis (H 37 Ra). Both compounds 26 and 35 given at a dose of 50 mg/kg for 5 weeks showed promising in vivo efficacy in a mouse model, with the 2'-deoxycytidine derivative being more effective than the uracil analogue and a reference drug o-cycloserine. These data indicated that there is a significant potential in this class of compounds.

  DOI：

  10.1021/jm100568q
• 作为产物：
  描述：

  1-戊炔 、 5-碘尿嘧啶 在 copper(l) iodide 、 四(三苯基膦)钯 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 18.0h， 以89%的产率得到5-pent-1-ynyluracil
  参考文献：
  名称：

  Inhibition of Mycobacterial Replication by Pyrimidines Possessing Various C-5 Functionalities and Related 2′-Deoxynucleoside Analogues Using in Vitro and in Vivo Models

  摘要：

  Tuberculosis (TB) has become an increasing problem since the emergence of human immunodeficiency virus and increasing appearance of drug-resistant strains. There is an urgent need to advance our knowledge and discover a new class of agents that are distinct than current therapies. Antimycobacterial activities of several 5-alkyl, 5-alkynyl, furanopyrimiclines and related 2'-deoxynucleosides were investigated against Mycobacterium tuberculosis. Compounds with 5-arylalkynyl substituents (23-26,33, 35) displayed potent in vitro antitubercular activity against Mycobacterium bovis and Mycobacterium tuberculosis. The in vivo activity of 5-(2-pyridylethyny1)-uracil (26) and its 2'-deoxycytidine analogue, 5-(2-pyridylethynyI)-2'-deoxycytidine (35), was assessed in BA LB/c mice infected with M. tuberculosis (H 37 Ra). Both compounds 26 and 35 given at a dose of 50 mg/kg for 5 weeks showed promising in vivo efficacy in a mouse model, with the 2'-deoxycytidine derivative being more effective than the uracil analogue and a reference drug o-cycloserine. These data indicated that there is a significant potential in this class of compounds.

  DOI：

  10.1021/jm100568q

文献信息

• Methods to Treat Cancer with 10-propargyl-10-deazaaminopterin and Methods for Assessing Cancer for Increased Sensitivity to 10-propargyl-10-deazaaminopterin
  申请人：O'Connor Owen A.

  公开号：US20080188479A1

  公开（公告）日：2008-08-07

  The present invention relates to a method for assessing the sensitivity of a patient's cancer to treatment with 10-propargyl-10-deazaaminopterin and a method for selecting a patient for treatment of cancer with 10-propargyl-10-deazaaminopterin, by determining the amount of a selected polypeptide expressed by the cancer and comparing the amount with the amount of the selected polypeptide expressed by a reference cancer, wherein the polypeptide includes a member of folate pathways within cells and may include at least one of reduced folate carrier-1 enzyme (RFC-1), dihydrofolate reductase (DHFR), folylpoly-gamma-glutamate synthetase (FPGS), thymidylate synthase (TS), γ-glutamyl hydrolase (GGH), and glycinamide ribonucleotide formyltransferase (GARFT). The present invention also relates to the use of 10-propargyl-10-deazaaminopterin in the treatment of multiple myeloma.

  本发明涉及一种评估患者癌症对10-丙炔基-10-脱氮基氨甲喋呤治疗敏感性的方法，以及一种通过确定癌细胞表达的特定多肽的数量并将其与参考癌症表达的特定多肽的数量进行比较来选择癌症患者进行10-丙炔基-10-脱氮基氨甲喋呤治疗的方法，其中多肽包括细胞内叶酸途径成员之一，可能包括至少一种还原型叶酸载体-1酶（RFC-1）、二氢叶酸还原酶（DHFR）、叶酰聚-γ-谷氨酰合酶（FPGS）、胸腺嘧啶合成酶（TS）、γ-谷氨酰水解酶（GGH）和甘氨酰核苷酸甲酰转移酶（GARFT）。本发明还涉及使用10-丙炔基-10-脱氮基氨甲喋呤治疗多发性骨髓瘤的方法。
• Nucleoside or nucleotides having novel unnatural bases and utilization of the same
  申请人：Hirao Ichiro

  公开号：US20060263771A1

  公开（公告）日：2006-11-23

  The object of the present invention is to provide a nucleoside or nucleotide having an unnatural base. The nucleoside or nucleotide of the present invention has a 5-substituted-2-oxo(1H)-pyridin-3-yl group as a base. Preferably, the 5-position of the above base is substituted with a substituent selected from the group consisting of the following: 1) a photoreactive group selected from iodine and bromine; 2) an alkenyl group, an alkynyl group or an amino group, or a derivative thereof; 3) biotin or a derivative thereof; and 4) a fluorescent molecule selected from fluorescein, 6-carboxyfluorescein, tetramethyl-6-carboxyrhodamine, and derivatives thereof.

  本发明的目的是提供一种具有非天然碱基的核苷或核苷酸。本发明的核苷或核苷酸具有5-取代-2-氧代（1H）-吡啶-3-基团作为碱基。优选地，上述碱基的5位被取代为以下群组中选择的取代基：1）光敏反应基团，选择自碘和溴；2）烯基基团，炔基基团或氨基基团或其衍生物；3）生物素或其衍生物；和4）荧光分子，选择自荧光素，6-羧基荧光素，四甲基-6-羧基罗丹明和其衍生物。
• Methods for Assessing Cancer for Increased Sensitivity to 10-Propargyl-10-Deazaaminopterin by Assessing Egfr Levels
  申请人：Pronk Gijsbertus J.

  公开号：US20100248249A1

  公开（公告）日：2010-09-30

  The present invention relates to a method for assessing the sensitivity of a patient's cancer to treatment with 10-propargyl-10-deazaminopterin and a method for selecting a patient for treatment of cancer with 10-propargyl-10-deazaminopterin, by determining the amount of a EGFR or other growth factor expressed by the cancer and comparing the amount with the amount of EGFR or other growth factor expressed by a reference cancer.

  本发明涉及一种评估患者癌症对10-丙炔基-10-去氨基葉酸治疗敏感性的方法，以及一种通过确定癌症表达的EGFR或其他生长因子的数量并将其与参考癌症表达的EGFR或其他生长因子的数量进行比较，选择患者进行10-丙炔基-10-去氨基葉酸治疗的方法。
• METHODS FOR ASSESSING CANCER FOR INCREASED SENSITIVITY TO 10-PROPARGYL-10-DEAZAAMINOPTERIN
  申请人：O'Connor Owen A.

  公开号：US20110111436A1

  公开（公告）日：2011-05-12

  Sensitivity of a patient's cancer to treatment with 10-propargyl-10-deazaaminopterin is assessed and patients are selected for treatment of cancer with 10-propargyl-10-deazaaminopterin, by determining the amount of a selected polypeptide expressed by the cancer and comparing the amount with the amount of the selected polypeptide expressed by a reference cancer. The polypeptide includes a member of a folate pathway polypeptide within a cell and may include at least one of reduced folate carrier-1 enzyme (RFC-1), dihydrofolate reductase (DHFR), folylpoly-gamma-glutamate synthetase (FPGS), thymidylate synthase (TS), γ-glutamyl hydrolase (GGH), and glycinamide ribonucleotide formyltransferase (GARFT).

  使用10-丙炔基-10-去氨基甲氨喋呤治疗患者癌症的敏感性是通过确定癌细胞表达的特定多肽的数量并将其与参考癌细胞表达的特定多肽的数量进行比较来评估的。该多肽包括细胞内叶酸途径多肽的成员，可能包括至少一种还原型叶酸载体1酶（RFC-1）、二氢叶酸还原酶（DHFR）、叶酰聚-γ-谷氨酰合成酶（FPGS）、胸腺嘧啶酸合酶（TS）、γ-谷氨酰肽水解酶（GGH）和甘氨酰核苷酸甲酰转移酶（GARFT）。
• METHODS AND REAGENTS FOR MULTIPLEXED ANALYSES OF PROTEINS
  申请人：Agilent Technologies, Inc.

  公开号：EP1464961A1

  公开（公告）日：2004-10-06

  Methods, devices and kits are disclosed for detecting one or more target proteins in a sample suspected of containing a plurality of the target proteins. An assay medium comprising the sample is incubated with a surface (11a) of a substrate (11) comprising a plurality of capture agents (20, 22, 24) bound to the surface in a predetermined arrangement or pattern. For each target protein, at least two capture agents specific for different binding sites on the target protein are employed. The two capture agents are disposed on the surface of the substrate in a spatial relationship so that both bind to a molecule of the target protein, preferably the same molecule of the target protein. The binding to the molecule of the target protein is usually substantially simultaneous. The assay medium is incubated under conditions for binding of the capture agents to the target proteins. The substrate is then examined for the presence of the target proteins.

  本发明公开了用于检测疑似含有多种目标蛋白的样品中的一种或多种目标蛋白的方法、装置和试剂盒。将含有样品的检测介质与基质（11）的表面（11a）孵育，基质（11）的表面按预定的排列或模式结合有多种捕获剂（20、22、24）。对于每种目标蛋白质，至少使用两种针对目标蛋白质上不同结合位点的特异性捕获剂。这两种捕获剂按一定的空间关系布置在基质表面上，使它们都与目标蛋白质的一个分子结合，最好是与目标蛋白质的同一个分子结合。与目标蛋白分子的结合通常基本上是同时进行的。检测介质在捕获剂与目标蛋白结合的条件下进行培养。然后检测底物中是否存在目标蛋白。