cyclo-3,5-di(tert-butyl)-6-fluoro chlorophosphite | 1026558-43-9

• 分子结构分类: 有机化合物 - 有机卤素化合物 - 芳基卤化物
• 英文名称: cyclo-3,5-di(tert-butyl)-6-fluoro chlorophosphite
• 英文别名: cycloSal-3,5-di(tert-butyl)-6-fluoro-chlorophosphite；4,6-di-tert-butyl-3-fluoro-2-(hydroxymethyl)phenol dioxaphosphinine；6,8-ditert-butyl-2-chloro-5-fluoro-4H-1,3,2-benzodioxaphosphinine
• CAS: 1026558-43-9
• 化学式: C₁₅H₂₁ClFO₂P
• 分子量: 318.756
• InChiKey: LZCAADPAQCEFSQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  18.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  cyclo-3,5-di(tert-butyl)-6-fluoro chlorophosphite 在 叔丁基过氧化氢 、 N,N-二异丙基乙胺 作用下， 以 癸烷 、 乙腈 为溶剂， 生成 1-[(2R,5S)-5-[(6,8-ditert-butyl-5-fluoro-2-oxo-4H-1,3,2$l^{5}-benzodioxaphosphinin-2-yl)oxymethyl]-2,5-dihydrofuran-2-yl]-5-methyl-pyrimidine-2,4-dione
  参考文献：
  名称：

  Interaction of cycloSal-Pronucleotides with Cholinesterases from Different Origins. A Structure−Activity Relationship

  摘要：

  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.

  DOI：

  10.1021/jm031032a
• 作为产物：
  描述：

  3-氟苯酚 在 吡啶 、 sodium hydroxide 、 硫酸 、 三氯化磷 作用下， 以 甲醇 、 乙醚 、 水 为溶剂， 反应 73.0h， 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

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。
• [EN] TARGETED RADIOLABELED COMPOUNDS AND THEIR USE FOR THE TREATMENT AND DIAGNOSIS OF CANCER<br/>[FR] COMPOSÉS RADIOMARQUÉS CIBLÉS, ET LEUR UTILISATION POUR LE TRAITEMENT ET LE DIAGNOSTIC DU CANCER
  申请人：UNIV NEBRASKA

  公开号：WO2011079245A1

  公开（公告）日：2011-06-30

  Method of using androgen receptor and/or butyrylcholinesterase targeted radiolabeled compounds, e.g., cycloSalingenyl pyrimidine nucleoside monophosphates, for the treatment and diagnosis of cancer.

  使用雄激素受体和/或丁酰胆碱酯酶靶向放射标记化合物的方法，例如环萨林基嘌呤核苷酸单磷酸，用于癌症的治疗和诊断。
• [EN] MIBG ANALOGS AND USES THEREOF<br/>[FR] ANALOGUES DE MIBG ET LEURS UTILISATIONS
  申请人：UNIV NEBRASKA

  公开号：WO2017053834A1

  公开（公告）日：2017-03-30

  Compounds and compositions for targeting cells expressing norepinephrine transporter, and methods of making and using the same. The compounds comprise MIBG analogs conjugated to active agents for treatment and/or diagnosis of various conditions, including neuroblastoma.

  用于靶向表达去甲肾上腺素转运蛋白的细胞的化合物和组合物，以及制备和使用这些化合物的方法。这些化合物包括与活性药物结合的MIBG类似物，用于治疗和/或诊断各种疾病，包括神经母细胞瘤。
• Norepinephrine-Transporter-Targeted and DNA-Co-Targeted Theranostic Guanidines
  作者：Zbigniew P. Kortylewicz、Donald W. Coulter、Guang Han、Janina Baranowska-Kortylewicz

  DOI：10.1021/acs.jmedchem.9b00437

  日期：2020.3.12

  This report describes syntheses, characterization, and biological properties of theranostic guanidines that target norepinephrine transporter and undergo intracellular processing, and subsequently their catabolites are efficiently incorporated into DNA of proliferating neuroblastoma cells. Radioactive guanidines are synthesized from 5-radioiodo-2′-deoxyuridine, a molecular radiotherapy platform with clinically

  即使采用积极治疗，高危神经母细胞瘤也经常复发。临床证据表明，增殖活动可预示不良预后。该报告描述了靶向去甲肾上腺素转运蛋白并经过细胞内加工的治疗性胍的合成，表征和生物学特性，随后将它们的分解代谢物有效地掺入了增殖性神经母细胞瘤细胞的DNA中。放射性胍是从5-radioiodo-2'-deoxyuridine（一种具有临床证明的最低毒性和DNA靶向特性的分子放射治疗平台）合成的。放射性胍转运到神经细胞瘤细胞是活性由细胞摄取的竞争抑制所指示的元-碘苄基胍。细胞内加工和DNA吸收的速率受试剂的分解代谢稳定性和细胞群体倍增时间的影响。放射毒性与DNA摄取量和暴露持续时间成正比。5- [ 125 I]碘-3'- O-（ε-胍基己酰基）-2'-脱氧尿苷在小鼠神经母细胞瘤模型中的生物分布显示出显着的肿瘤保留放射性。神经母细胞瘤异种移植物响应于该剂的临床上可达到的剂量而消退。
• Radiologic Agents for Monitoring Alzheimer's Disease Progression and Evaluating a Response to Therapy and Processes for the Preparation of Such Agents
  申请人：Kortylewicz Zbigniew P.

  公开号：US20090117041A1

  公开（公告）日：2009-05-07

  Disclosed are certain cycloSalingenyl pyrimidine nucleoside monophosphates comprising positron emitters or gamma-emitting radiohalides, uses thereof for monitoring Alzheimer's disease progression and evaluating response to therapy and process for their preparation.

  本文披露了包含正电子发射体或伽马辐射放射性卤化物的某些环丝氨基嘧啶核苷酸单磷酸盐，其用于监测阿尔茨海默病的进展并评估对治疗的反应，以及它们的制备过程。