3,5-di(tert-butyl)-6-fluorosalicyl alcohol | 660390-78-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 3,5-di(tert-butyl)-6-fluorosalicyl alcohol
• 英文别名: 3,5-bis-tert-butyl-6-fluorosalicyl alcohol；3,5-Bis(1,1-dimethylethyl)-2-fluoro-6-hydroxybenzenemethanol；4,6-ditert-butyl-3-fluoro-2-(hydroxymethyl)phenol
• CAS: 660390-78-3
• 化学式: C₁₅H₂₃FO₂
• 分子量: 254.345
• InChiKey: PQWAJHKDTGPXMB-UHFFFAOYSA-N

物化性质

• 沸点：
  302.8±37.0 °C(Predicted)
• 密度：
  1.063±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  40.5
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3,5-di(tert-butyl)-6-fluorosalicyl alcohol 在 吡啶 、 三氯化磷 作用下， 以 乙醚 为溶剂， 生成 cyclo-3,5-di(tert-butyl)-6-fluoro chlorophosphite
  参考文献：
  名称：

  3,5-Di-(tert-Butyl)-6-fluoro-cycloSal-d4TMP-一种掩蔽基团显着改善的前核苷酸

  摘要：

  已经开发了一种新的、显着改进的 cycloSal 掩蔽组。这个新组结合了四种理想的特性，并已连接到抗 HIV 药物 2',3'-dideoxy-2',3'-didehydrothymidine (d4T, 1) 上以产生 3,5-(di-tert-butyl) -6-氟-环Sal-d4TMP (2i)。这种磷酸三酯具有合理的化学半衰期，高度选择性地释放 d4TMP，对丁酰胆碱酯酶 (BChE) 的抑制作用很差（如果有的话），并实现了 TK 旁路。(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)

  DOI：

  10.1002/ejoc.200300537
• 作为产物：
  描述：

  3-氟苯酚 在 sodium hydroxide 、 硫酸 作用下， 以 甲醇 、 水 为溶剂， 反应 73.0h， 生成 3,5-di(tert-butyl)-6-fluorosalicyl alcohol
  参考文献：
  名称：

  3,5-Di-(tert-Butyl)-6-fluoro-cycloSal-d4TMP-一种掩蔽基团显着改善的前核苷酸

  摘要：

  已经开发了一种新的、显着改进的 cycloSal 掩蔽组。这个新组结合了四种理想的特性，并已连接到抗 HIV 药物 2',3'-dideoxy-2',3'-didehydrothymidine (d4T, 1) 上以产生 3,5-(di-tert-butyl) -6-氟-环Sal-d4TMP (2i)。这种磷酸三酯具有合理的化学半衰期，高度选择性地释放 d4TMP，对丁酰胆碱酯酶 (BChE) 的抑制作用很差（如果有的话），并实现了 TK 旁路。(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)

  DOI：

  10.1002/ejoc.200300537

文献信息

• [EN] PRODRUGS OF AZACITIDINE 5'-PHOSPHATE<br/>[FR] PROMÉDICAMENTS DE 5'-PHOSPHATE D'AZACITIDINE
  申请人：SYNDAX PHARMACEUTICALS INC

  公开号：WO2011153374A1

  公开（公告）日：2011-12-08

  The present disclosure relates to analogs or derivatives of azacitidine with improved pharmaceutical properties and methods for the treatment of proliferative disease utilizing said analogs or derivatives.

  本公开涉及具有改善药物性质的氮杂胞苷类似物或衍生物，以及利用这些类似物或衍生物治疗增殖性疾病的方法。
• Interaction of <i>cyclo</i>Sal-Pronucleotides with Cholinesterases from Different Origins. A Structure−Activity Relationship
  作者：Chris Meier、Christian Ducho、Ulf Görbig、Robert Esnouf、Jan Balzarini

  DOI：10.1021/jm031032a

  日期：2004.5.1

  A large number of cycloSal-nucleotide triesters 1-49 have been studied concerning their ability to inhibit cholinesterases of different origins as well as to inhibit HIV replication in cell culture. It was shown that none of the triesters showed inhibitory effects against human acetylcholinesterase (AChE; isolated enzyme) as well as against AChE from beef erythrocytes and calf serum. In contrast, inhibition of butyrylcholinesterase (BChE) has been observed for some triesters in human and mouse serum. cycloSal pronucleotides showed strong competitive inhibition with respect to the substrate acetylcholine chloride (K-i/K-m: similar to2 x 10(-5)) and acted by time-dependent irreversible inhibition of the human serum BChE. Detailed studies demonstrated that the inhibitory effect against BChE is dependent on the nucleoside analogue, the substitution pattern of the cycloSal-moiety, and particularly on the stereochemistry at the phosphorus atom. Structural requirements to avoid the inhibition of BChE by cycloSal-nucleotide triesters have been elucidated in the reported study.
• Radiolabeled Cyclosaligenyl Monophosphates of 5-Iodo-2′-deoxyuridine, 5-Iodo-3′-fluoro-2′,3′-dideoxyuridine, and 3′-Fluorothymidine for Molecular Radiotherapy of Cancer: Synthesis and Biological Evaluation
  作者：Zbigniew P. Kortylewicz、Yu Kimura、Kotaro Inoue、Elizabeth Mack、Janina Baranowska-Kortylewicz

  DOI：10.1021/jm201482p

  日期：2012.3.22

  Targeted molecular radiotherapy opens unprecedented opportunities to eradicate cancer cells with minimal irradiation of normal tissues. Described in this study are radioactive cyclosaligenyl monophosphates designed to deliver lethal doses of radiation to cancer cells. These compounds can be radiolabeled with SPECT- and PET-compatible radionuclides as well as radionuclides suitable for Auger electron therapies. This characteristic provides an avenue for the personalized and comprehensive treatment strategy that comprises diagnostic imaging to identify sites of disease, followed by the targeted molecular radiotherapy based on the imaging results. The developed radiosynthetic methods produce no-carrier-added products with high radiochemical yield and purity. The interaction of these compounds with their target, butyrylcholinesterase, depends on the stereochemistry around the P atom. 1050 values are in the nanomolar range. In vitro studies indicate that radiation doses delivered to the cell nucleus are sufficient to kill cells of several difficult to treat malignancies including glioblastoma and ovarian and colorectal cancers.